Divergent immune microenvironments in two tumor nodules from a patient with mismatch repair-deficient prostate cancer
Abstract Patients with prostate cancer (PC) generally do not respond favorably to immune checkpoint inhibitors, which may be due to a low abundance of tumor-infiltrating lymphocytes even when mutational load is high. Here, we identified a patient who presented with high-grade primary prostate cancer...
Ausführliche Beschreibung
Gespeichert in:
| Autor*in: |
Hannah E. Bergom [verfasserIn] Laura A. Sena [verfasserIn] Abderrahman Day [verfasserIn] Benjamin Miller [verfasserIn] Carly D. Miller [verfasserIn] John R. Lozada [verfasserIn] Nicholas Zorko [verfasserIn] Jinhua Wang [verfasserIn] Eugene Shenderov [verfasserIn] Francisco Pereira Lobo [verfasserIn] Fernanda Caramella-Pereira [verfasserIn] Luigi Marchionni [verfasserIn] Charles G. Drake [verfasserIn] Tamara Lotan [verfasserIn] Angelo M. De Marzo [verfasserIn] Justin Hwang [verfasserIn] Emmanuel S. Antonarakis [verfasserIn] |
|---|
| Format: |
E-Artikel |
|---|---|
| Sprache: |
Englisch |
| Erschienen: |
2024 |
|---|
| Übergeordnetes Werk: |
In: npj Genomic Medicine - Nature Portfolio, 2016, 9(2024), 1, Seite 9 |
|---|---|
| Übergeordnetes Werk: |
volume:9 ; year:2024 ; number:1 ; pages:9 |
| Links: |
|---|
| DOI / URN: |
10.1038/s41525-024-00392-1 |
|---|
| Katalog-ID: |
DOAJ092212646 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | DOAJ092212646 | ||
| 003 | DE-627 | ||
| 005 | 20240414094250.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 240412s2024 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1038/s41525-024-00392-1 |2 doi | |
| 035 | |a (DE-627)DOAJ092212646 | ||
| 035 | |a (DE-599)DOAJa63fc47e643a46939677c01b1b4e10df | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 050 | 0 | |a QH426-470 | |
| 100 | 0 | |a Hannah E. Bergom |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Divergent immune microenvironments in two tumor nodules from a patient with mismatch repair-deficient prostate cancer |
| 264 | 1 | |c 2024 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a Computermedien |b c |2 rdamedia | ||
| 338 | |a Online-Ressource |b cr |2 rdacarrier | ||
| 520 | |a Abstract Patients with prostate cancer (PC) generally do not respond favorably to immune checkpoint inhibitors, which may be due to a low abundance of tumor-infiltrating lymphocytes even when mutational load is high. Here, we identified a patient who presented with high-grade primary prostate cancer with two adjacent tumor nodules. While both nodules were mismatch repair-deficient (MMRd), exhibited pathogenic MSH2 and MSH6 alterations, had a high tumor mutational burden (TMB), and demonstrated high microsatellite instability (MSI), they had markedly distinct immune phenotypes. The first displayed a dense infiltrate of lymphocytes (“hot nodule”), while the second displayed significantly fewer infiltrating lymphocytes (“cold nodule”). Whole-exome DNA analysis found that both nodules shared many identical mutations, indicating that they were derived from a single clone. However, the cold nodule appeared to be sub-clonal relative to the hot nodule, suggesting divergent evolution of the cold nodule from the hot nodule. Whole-transcriptome RNA analysis found that the cold nodule demonstrated lower expression of genes related to antigen presentation (HLA) and, paradoxically, classical tumor immune tolerance markers such as PD-L1 (CD274) and CTLA-4. Immune cell deconvolution suggested that the hot nodule was enriched not only in CD8+ and CD4 + T lymphocytes, but also in M1 macrophages, activated NK cells, and γδ T cells compared to the cold nodule. This case highlights that MMRd/TMB-high PC can evolve to minimize an anti-tumor immune response, and nominates downregulation of antigen presentation machinery (HLA loss) as a potential mechanism of adaptive immune evasion in PC. | ||
| 653 | 0 | |a Medicine | |
| 653 | 0 | |a R | |
| 653 | 0 | |a Genetics | |
| 700 | 0 | |a Laura A. Sena |e verfasserin |4 aut | |
| 700 | 0 | |a Abderrahman Day |e verfasserin |4 aut | |
| 700 | 0 | |a Benjamin Miller |e verfasserin |4 aut | |
| 700 | 0 | |a Carly D. Miller |e verfasserin |4 aut | |
| 700 | 0 | |a John R. Lozada |e verfasserin |4 aut | |
| 700 | 0 | |a Nicholas Zorko |e verfasserin |4 aut | |
| 700 | 0 | |a Jinhua Wang |e verfasserin |4 aut | |
| 700 | 0 | |a Eugene Shenderov |e verfasserin |4 aut | |
| 700 | 0 | |a Francisco Pereira Lobo |e verfasserin |4 aut | |
| 700 | 0 | |a Fernanda Caramella-Pereira |e verfasserin |4 aut | |
| 700 | 0 | |a Luigi Marchionni |e verfasserin |4 aut | |
| 700 | 0 | |a Charles G. Drake |e verfasserin |4 aut | |
| 700 | 0 | |a Tamara Lotan |e verfasserin |4 aut | |
| 700 | 0 | |a Angelo M. De Marzo |e verfasserin |4 aut | |
| 700 | 0 | |a Justin Hwang |e verfasserin |4 aut | |
| 700 | 0 | |a Emmanuel S. Antonarakis |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i In |t npj Genomic Medicine |d Nature Portfolio, 2016 |g 9(2024), 1, Seite 9 |w (DE-627)820061727 |w (DE-600)2813848-X |x 20567944 |7 nnns |
| 773 | 1 | 8 | |g volume:9 |g year:2024 |g number:1 |g pages:9 |
| 856 | 4 | 0 | |u https://doi.org/10.1038/s41525-024-00392-1 |z kostenfrei |
| 856 | 4 | 0 | |u https://doaj.org/article/a63fc47e643a46939677c01b1b4e10df |z kostenfrei |
| 856 | 4 | 0 | |u https://doi.org/10.1038/s41525-024-00392-1 |z kostenfrei |
| 856 | 4 | 2 | |u https://doaj.org/toc/2056-7944 |y Journal toc |z kostenfrei |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a SYSFLAG_A | ||
| 912 | |a GBV_DOAJ | ||
| 912 | |a GBV_ILN_20 | ||
| 912 | |a GBV_ILN_22 | ||
| 912 | |a GBV_ILN_23 | ||
| 912 | |a GBV_ILN_24 | ||
| 912 | |a GBV_ILN_39 | ||
| 912 | |a GBV_ILN_40 | ||
| 912 | |a GBV_ILN_60 | ||
| 912 | |a GBV_ILN_62 | ||
| 912 | |a GBV_ILN_63 | ||
| 912 | |a GBV_ILN_65 | ||
| 912 | |a GBV_ILN_69 | ||
| 912 | |a GBV_ILN_73 | ||
| 912 | |a GBV_ILN_74 | ||
| 912 | |a GBV_ILN_95 | ||
| 912 | |a GBV_ILN_105 | ||
| 912 | |a GBV_ILN_110 | ||
| 912 | |a GBV_ILN_151 | ||
| 912 | |a GBV_ILN_161 | ||
| 912 | |a GBV_ILN_170 | ||
| 912 | |a GBV_ILN_206 | ||
| 912 | |a GBV_ILN_213 | ||
| 912 | |a GBV_ILN_230 | ||
| 912 | |a GBV_ILN_285 | ||
| 912 | |a GBV_ILN_293 | ||
| 912 | |a GBV_ILN_602 | ||
| 912 | |a GBV_ILN_2014 | ||
| 912 | |a GBV_ILN_4012 | ||
| 912 | |a GBV_ILN_4037 | ||
| 912 | |a GBV_ILN_4112 | ||
| 912 | |a GBV_ILN_4125 | ||
| 912 | |a GBV_ILN_4126 | ||
| 912 | |a GBV_ILN_4249 | ||
| 912 | |a GBV_ILN_4305 | ||
| 912 | |a GBV_ILN_4306 | ||
| 912 | |a GBV_ILN_4307 | ||
| 912 | |a GBV_ILN_4313 | ||
| 912 | |a GBV_ILN_4322 | ||
| 912 | |a GBV_ILN_4323 | ||
| 912 | |a GBV_ILN_4324 | ||
| 912 | |a GBV_ILN_4325 | ||
| 912 | |a GBV_ILN_4338 | ||
| 912 | |a GBV_ILN_4367 | ||
| 912 | |a GBV_ILN_4700 | ||
| 951 | |a AR | ||
| 952 | |d 9 |j 2024 |e 1 |h 9 | ||
| author_variant |
h e b heb l a s las a d ad b m bm c d m cdm j r l jrl n z nz j w jw e s es f p l fpl f c p fcp l m lm c g d cgd t l tl a m d m amdm j h jh e s a esa |
|---|---|
| matchkey_str |
article:20567944:2024----::iegnimnmconiomnsnwtmrouefoaainwtmsacr |
| hierarchy_sort_str |
2024 |
| callnumber-subject-code |
QH |
| publishDate |
2024 |
| allfields |
10.1038/s41525-024-00392-1 doi (DE-627)DOAJ092212646 (DE-599)DOAJa63fc47e643a46939677c01b1b4e10df DE-627 ger DE-627 rakwb eng QH426-470 Hannah E. Bergom verfasserin aut Divergent immune microenvironments in two tumor nodules from a patient with mismatch repair-deficient prostate cancer 2024 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Patients with prostate cancer (PC) generally do not respond favorably to immune checkpoint inhibitors, which may be due to a low abundance of tumor-infiltrating lymphocytes even when mutational load is high. Here, we identified a patient who presented with high-grade primary prostate cancer with two adjacent tumor nodules. While both nodules were mismatch repair-deficient (MMRd), exhibited pathogenic MSH2 and MSH6 alterations, had a high tumor mutational burden (TMB), and demonstrated high microsatellite instability (MSI), they had markedly distinct immune phenotypes. The first displayed a dense infiltrate of lymphocytes (“hot nodule”), while the second displayed significantly fewer infiltrating lymphocytes (“cold nodule”). Whole-exome DNA analysis found that both nodules shared many identical mutations, indicating that they were derived from a single clone. However, the cold nodule appeared to be sub-clonal relative to the hot nodule, suggesting divergent evolution of the cold nodule from the hot nodule. Whole-transcriptome RNA analysis found that the cold nodule demonstrated lower expression of genes related to antigen presentation (HLA) and, paradoxically, classical tumor immune tolerance markers such as PD-L1 (CD274) and CTLA-4. Immune cell deconvolution suggested that the hot nodule was enriched not only in CD8+ and CD4 + T lymphocytes, but also in M1 macrophages, activated NK cells, and γδ T cells compared to the cold nodule. This case highlights that MMRd/TMB-high PC can evolve to minimize an anti-tumor immune response, and nominates downregulation of antigen presentation machinery (HLA loss) as a potential mechanism of adaptive immune evasion in PC. Medicine R Genetics Laura A. Sena verfasserin aut Abderrahman Day verfasserin aut Benjamin Miller verfasserin aut Carly D. Miller verfasserin aut John R. Lozada verfasserin aut Nicholas Zorko verfasserin aut Jinhua Wang verfasserin aut Eugene Shenderov verfasserin aut Francisco Pereira Lobo verfasserin aut Fernanda Caramella-Pereira verfasserin aut Luigi Marchionni verfasserin aut Charles G. Drake verfasserin aut Tamara Lotan verfasserin aut Angelo M. De Marzo verfasserin aut Justin Hwang verfasserin aut Emmanuel S. Antonarakis verfasserin aut In npj Genomic Medicine Nature Portfolio, 2016 9(2024), 1, Seite 9 (DE-627)820061727 (DE-600)2813848-X 20567944 nnns volume:9 year:2024 number:1 pages:9 https://doi.org/10.1038/s41525-024-00392-1 kostenfrei https://doaj.org/article/a63fc47e643a46939677c01b1b4e10df kostenfrei https://doi.org/10.1038/s41525-024-00392-1 kostenfrei https://doaj.org/toc/2056-7944 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 9 2024 1 9 |
| spelling |
10.1038/s41525-024-00392-1 doi (DE-627)DOAJ092212646 (DE-599)DOAJa63fc47e643a46939677c01b1b4e10df DE-627 ger DE-627 rakwb eng QH426-470 Hannah E. Bergom verfasserin aut Divergent immune microenvironments in two tumor nodules from a patient with mismatch repair-deficient prostate cancer 2024 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Patients with prostate cancer (PC) generally do not respond favorably to immune checkpoint inhibitors, which may be due to a low abundance of tumor-infiltrating lymphocytes even when mutational load is high. Here, we identified a patient who presented with high-grade primary prostate cancer with two adjacent tumor nodules. While both nodules were mismatch repair-deficient (MMRd), exhibited pathogenic MSH2 and MSH6 alterations, had a high tumor mutational burden (TMB), and demonstrated high microsatellite instability (MSI), they had markedly distinct immune phenotypes. The first displayed a dense infiltrate of lymphocytes (“hot nodule”), while the second displayed significantly fewer infiltrating lymphocytes (“cold nodule”). Whole-exome DNA analysis found that both nodules shared many identical mutations, indicating that they were derived from a single clone. However, the cold nodule appeared to be sub-clonal relative to the hot nodule, suggesting divergent evolution of the cold nodule from the hot nodule. Whole-transcriptome RNA analysis found that the cold nodule demonstrated lower expression of genes related to antigen presentation (HLA) and, paradoxically, classical tumor immune tolerance markers such as PD-L1 (CD274) and CTLA-4. Immune cell deconvolution suggested that the hot nodule was enriched not only in CD8+ and CD4 + T lymphocytes, but also in M1 macrophages, activated NK cells, and γδ T cells compared to the cold nodule. This case highlights that MMRd/TMB-high PC can evolve to minimize an anti-tumor immune response, and nominates downregulation of antigen presentation machinery (HLA loss) as a potential mechanism of adaptive immune evasion in PC. Medicine R Genetics Laura A. Sena verfasserin aut Abderrahman Day verfasserin aut Benjamin Miller verfasserin aut Carly D. Miller verfasserin aut John R. Lozada verfasserin aut Nicholas Zorko verfasserin aut Jinhua Wang verfasserin aut Eugene Shenderov verfasserin aut Francisco Pereira Lobo verfasserin aut Fernanda Caramella-Pereira verfasserin aut Luigi Marchionni verfasserin aut Charles G. Drake verfasserin aut Tamara Lotan verfasserin aut Angelo M. De Marzo verfasserin aut Justin Hwang verfasserin aut Emmanuel S. Antonarakis verfasserin aut In npj Genomic Medicine Nature Portfolio, 2016 9(2024), 1, Seite 9 (DE-627)820061727 (DE-600)2813848-X 20567944 nnns volume:9 year:2024 number:1 pages:9 https://doi.org/10.1038/s41525-024-00392-1 kostenfrei https://doaj.org/article/a63fc47e643a46939677c01b1b4e10df kostenfrei https://doi.org/10.1038/s41525-024-00392-1 kostenfrei https://doaj.org/toc/2056-7944 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 9 2024 1 9 |
| allfields_unstemmed |
10.1038/s41525-024-00392-1 doi (DE-627)DOAJ092212646 (DE-599)DOAJa63fc47e643a46939677c01b1b4e10df DE-627 ger DE-627 rakwb eng QH426-470 Hannah E. Bergom verfasserin aut Divergent immune microenvironments in two tumor nodules from a patient with mismatch repair-deficient prostate cancer 2024 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Patients with prostate cancer (PC) generally do not respond favorably to immune checkpoint inhibitors, which may be due to a low abundance of tumor-infiltrating lymphocytes even when mutational load is high. Here, we identified a patient who presented with high-grade primary prostate cancer with two adjacent tumor nodules. While both nodules were mismatch repair-deficient (MMRd), exhibited pathogenic MSH2 and MSH6 alterations, had a high tumor mutational burden (TMB), and demonstrated high microsatellite instability (MSI), they had markedly distinct immune phenotypes. The first displayed a dense infiltrate of lymphocytes (“hot nodule”), while the second displayed significantly fewer infiltrating lymphocytes (“cold nodule”). Whole-exome DNA analysis found that both nodules shared many identical mutations, indicating that they were derived from a single clone. However, the cold nodule appeared to be sub-clonal relative to the hot nodule, suggesting divergent evolution of the cold nodule from the hot nodule. Whole-transcriptome RNA analysis found that the cold nodule demonstrated lower expression of genes related to antigen presentation (HLA) and, paradoxically, classical tumor immune tolerance markers such as PD-L1 (CD274) and CTLA-4. Immune cell deconvolution suggested that the hot nodule was enriched not only in CD8+ and CD4 + T lymphocytes, but also in M1 macrophages, activated NK cells, and γδ T cells compared to the cold nodule. This case highlights that MMRd/TMB-high PC can evolve to minimize an anti-tumor immune response, and nominates downregulation of antigen presentation machinery (HLA loss) as a potential mechanism of adaptive immune evasion in PC. Medicine R Genetics Laura A. Sena verfasserin aut Abderrahman Day verfasserin aut Benjamin Miller verfasserin aut Carly D. Miller verfasserin aut John R. Lozada verfasserin aut Nicholas Zorko verfasserin aut Jinhua Wang verfasserin aut Eugene Shenderov verfasserin aut Francisco Pereira Lobo verfasserin aut Fernanda Caramella-Pereira verfasserin aut Luigi Marchionni verfasserin aut Charles G. Drake verfasserin aut Tamara Lotan verfasserin aut Angelo M. De Marzo verfasserin aut Justin Hwang verfasserin aut Emmanuel S. Antonarakis verfasserin aut In npj Genomic Medicine Nature Portfolio, 2016 9(2024), 1, Seite 9 (DE-627)820061727 (DE-600)2813848-X 20567944 nnns volume:9 year:2024 number:1 pages:9 https://doi.org/10.1038/s41525-024-00392-1 kostenfrei https://doaj.org/article/a63fc47e643a46939677c01b1b4e10df kostenfrei https://doi.org/10.1038/s41525-024-00392-1 kostenfrei https://doaj.org/toc/2056-7944 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 9 2024 1 9 |
| allfieldsGer |
10.1038/s41525-024-00392-1 doi (DE-627)DOAJ092212646 (DE-599)DOAJa63fc47e643a46939677c01b1b4e10df DE-627 ger DE-627 rakwb eng QH426-470 Hannah E. Bergom verfasserin aut Divergent immune microenvironments in two tumor nodules from a patient with mismatch repair-deficient prostate cancer 2024 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Patients with prostate cancer (PC) generally do not respond favorably to immune checkpoint inhibitors, which may be due to a low abundance of tumor-infiltrating lymphocytes even when mutational load is high. Here, we identified a patient who presented with high-grade primary prostate cancer with two adjacent tumor nodules. While both nodules were mismatch repair-deficient (MMRd), exhibited pathogenic MSH2 and MSH6 alterations, had a high tumor mutational burden (TMB), and demonstrated high microsatellite instability (MSI), they had markedly distinct immune phenotypes. The first displayed a dense infiltrate of lymphocytes (“hot nodule”), while the second displayed significantly fewer infiltrating lymphocytes (“cold nodule”). Whole-exome DNA analysis found that both nodules shared many identical mutations, indicating that they were derived from a single clone. However, the cold nodule appeared to be sub-clonal relative to the hot nodule, suggesting divergent evolution of the cold nodule from the hot nodule. Whole-transcriptome RNA analysis found that the cold nodule demonstrated lower expression of genes related to antigen presentation (HLA) and, paradoxically, classical tumor immune tolerance markers such as PD-L1 (CD274) and CTLA-4. Immune cell deconvolution suggested that the hot nodule was enriched not only in CD8+ and CD4 + T lymphocytes, but also in M1 macrophages, activated NK cells, and γδ T cells compared to the cold nodule. This case highlights that MMRd/TMB-high PC can evolve to minimize an anti-tumor immune response, and nominates downregulation of antigen presentation machinery (HLA loss) as a potential mechanism of adaptive immune evasion in PC. Medicine R Genetics Laura A. Sena verfasserin aut Abderrahman Day verfasserin aut Benjamin Miller verfasserin aut Carly D. Miller verfasserin aut John R. Lozada verfasserin aut Nicholas Zorko verfasserin aut Jinhua Wang verfasserin aut Eugene Shenderov verfasserin aut Francisco Pereira Lobo verfasserin aut Fernanda Caramella-Pereira verfasserin aut Luigi Marchionni verfasserin aut Charles G. Drake verfasserin aut Tamara Lotan verfasserin aut Angelo M. De Marzo verfasserin aut Justin Hwang verfasserin aut Emmanuel S. Antonarakis verfasserin aut In npj Genomic Medicine Nature Portfolio, 2016 9(2024), 1, Seite 9 (DE-627)820061727 (DE-600)2813848-X 20567944 nnns volume:9 year:2024 number:1 pages:9 https://doi.org/10.1038/s41525-024-00392-1 kostenfrei https://doaj.org/article/a63fc47e643a46939677c01b1b4e10df kostenfrei https://doi.org/10.1038/s41525-024-00392-1 kostenfrei https://doaj.org/toc/2056-7944 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 9 2024 1 9 |
| allfieldsSound |
10.1038/s41525-024-00392-1 doi (DE-627)DOAJ092212646 (DE-599)DOAJa63fc47e643a46939677c01b1b4e10df DE-627 ger DE-627 rakwb eng QH426-470 Hannah E. Bergom verfasserin aut Divergent immune microenvironments in two tumor nodules from a patient with mismatch repair-deficient prostate cancer 2024 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Patients with prostate cancer (PC) generally do not respond favorably to immune checkpoint inhibitors, which may be due to a low abundance of tumor-infiltrating lymphocytes even when mutational load is high. Here, we identified a patient who presented with high-grade primary prostate cancer with two adjacent tumor nodules. While both nodules were mismatch repair-deficient (MMRd), exhibited pathogenic MSH2 and MSH6 alterations, had a high tumor mutational burden (TMB), and demonstrated high microsatellite instability (MSI), they had markedly distinct immune phenotypes. The first displayed a dense infiltrate of lymphocytes (“hot nodule”), while the second displayed significantly fewer infiltrating lymphocytes (“cold nodule”). Whole-exome DNA analysis found that both nodules shared many identical mutations, indicating that they were derived from a single clone. However, the cold nodule appeared to be sub-clonal relative to the hot nodule, suggesting divergent evolution of the cold nodule from the hot nodule. Whole-transcriptome RNA analysis found that the cold nodule demonstrated lower expression of genes related to antigen presentation (HLA) and, paradoxically, classical tumor immune tolerance markers such as PD-L1 (CD274) and CTLA-4. Immune cell deconvolution suggested that the hot nodule was enriched not only in CD8+ and CD4 + T lymphocytes, but also in M1 macrophages, activated NK cells, and γδ T cells compared to the cold nodule. This case highlights that MMRd/TMB-high PC can evolve to minimize an anti-tumor immune response, and nominates downregulation of antigen presentation machinery (HLA loss) as a potential mechanism of adaptive immune evasion in PC. Medicine R Genetics Laura A. Sena verfasserin aut Abderrahman Day verfasserin aut Benjamin Miller verfasserin aut Carly D. Miller verfasserin aut John R. Lozada verfasserin aut Nicholas Zorko verfasserin aut Jinhua Wang verfasserin aut Eugene Shenderov verfasserin aut Francisco Pereira Lobo verfasserin aut Fernanda Caramella-Pereira verfasserin aut Luigi Marchionni verfasserin aut Charles G. Drake verfasserin aut Tamara Lotan verfasserin aut Angelo M. De Marzo verfasserin aut Justin Hwang verfasserin aut Emmanuel S. Antonarakis verfasserin aut In npj Genomic Medicine Nature Portfolio, 2016 9(2024), 1, Seite 9 (DE-627)820061727 (DE-600)2813848-X 20567944 nnns volume:9 year:2024 number:1 pages:9 https://doi.org/10.1038/s41525-024-00392-1 kostenfrei https://doaj.org/article/a63fc47e643a46939677c01b1b4e10df kostenfrei https://doi.org/10.1038/s41525-024-00392-1 kostenfrei https://doaj.org/toc/2056-7944 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 9 2024 1 9 |
| language |
English |
| source |
In npj Genomic Medicine 9(2024), 1, Seite 9 volume:9 year:2024 number:1 pages:9 |
| sourceStr |
In npj Genomic Medicine 9(2024), 1, Seite 9 volume:9 year:2024 number:1 pages:9 |
| format_phy_str_mv |
Article |
| institution |
findex.gbv.de |
| topic_facet |
Medicine R Genetics |
| isfreeaccess_bool |
true |
| container_title |
npj Genomic Medicine |
| authorswithroles_txt_mv |
Hannah E. Bergom @@aut@@ Laura A. Sena @@aut@@ Abderrahman Day @@aut@@ Benjamin Miller @@aut@@ Carly D. Miller @@aut@@ John R. Lozada @@aut@@ Nicholas Zorko @@aut@@ Jinhua Wang @@aut@@ Eugene Shenderov @@aut@@ Francisco Pereira Lobo @@aut@@ Fernanda Caramella-Pereira @@aut@@ Luigi Marchionni @@aut@@ Charles G. Drake @@aut@@ Tamara Lotan @@aut@@ Angelo M. De Marzo @@aut@@ Justin Hwang @@aut@@ Emmanuel S. Antonarakis @@aut@@ |
| publishDateDaySort_date |
2024-01-01T00:00:00Z |
| hierarchy_top_id |
820061727 |
| id |
DOAJ092212646 |
| language_de |
englisch |
| fullrecord |
<?xml version="1.0" encoding="UTF-8"?><collection xmlns="http://www.loc.gov/MARC21/slim"><record><leader>01000caa a22002652 4500</leader><controlfield tag="001">DOAJ092212646</controlfield><controlfield tag="003">DE-627</controlfield><controlfield tag="005">20240414094250.0</controlfield><controlfield tag="007">cr uuu---uuuuu</controlfield><controlfield tag="008">240412s2024 xx |||||o 00| ||eng c</controlfield><datafield tag="024" ind1="7" ind2=" "><subfield code="a">10.1038/s41525-024-00392-1</subfield><subfield code="2">doi</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-627)DOAJ092212646</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-599)DOAJa63fc47e643a46939677c01b1b4e10df</subfield></datafield><datafield tag="040" ind1=" " ind2=" "><subfield code="a">DE-627</subfield><subfield code="b">ger</subfield><subfield code="c">DE-627</subfield><subfield code="e">rakwb</subfield></datafield><datafield tag="041" ind1=" " ind2=" "><subfield code="a">eng</subfield></datafield><datafield tag="050" ind1=" " ind2="0"><subfield code="a">QH426-470</subfield></datafield><datafield tag="100" ind1="0" ind2=" "><subfield code="a">Hannah E. Bergom</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">Divergent immune microenvironments in two tumor nodules from a patient with mismatch repair-deficient prostate cancer</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">2024</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="a">Text</subfield><subfield code="b">txt</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="a">Computermedien</subfield><subfield code="b">c</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="a">Online-Ressource</subfield><subfield code="b">cr</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Abstract Patients with prostate cancer (PC) generally do not respond favorably to immune checkpoint inhibitors, which may be due to a low abundance of tumor-infiltrating lymphocytes even when mutational load is high. Here, we identified a patient who presented with high-grade primary prostate cancer with two adjacent tumor nodules. While both nodules were mismatch repair-deficient (MMRd), exhibited pathogenic MSH2 and MSH6 alterations, had a high tumor mutational burden (TMB), and demonstrated high microsatellite instability (MSI), they had markedly distinct immune phenotypes. The first displayed a dense infiltrate of lymphocytes (“hot nodule”), while the second displayed significantly fewer infiltrating lymphocytes (“cold nodule”). Whole-exome DNA analysis found that both nodules shared many identical mutations, indicating that they were derived from a single clone. However, the cold nodule appeared to be sub-clonal relative to the hot nodule, suggesting divergent evolution of the cold nodule from the hot nodule. Whole-transcriptome RNA analysis found that the cold nodule demonstrated lower expression of genes related to antigen presentation (HLA) and, paradoxically, classical tumor immune tolerance markers such as PD-L1 (CD274) and CTLA-4. Immune cell deconvolution suggested that the hot nodule was enriched not only in CD8+ and CD4 + T lymphocytes, but also in M1 macrophages, activated NK cells, and γδ T cells compared to the cold nodule. This case highlights that MMRd/TMB-high PC can evolve to minimize an anti-tumor immune response, and nominates downregulation of antigen presentation machinery (HLA loss) as a potential mechanism of adaptive immune evasion in PC.</subfield></datafield><datafield tag="653" ind1=" " ind2="0"><subfield code="a">Medicine</subfield></datafield><datafield tag="653" ind1=" " ind2="0"><subfield code="a">R</subfield></datafield><datafield tag="653" ind1=" " ind2="0"><subfield code="a">Genetics</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Laura A. Sena</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Abderrahman Day</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Benjamin Miller</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Carly D. Miller</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">John R. Lozada</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Nicholas Zorko</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Jinhua Wang</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Eugene Shenderov</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Francisco Pereira Lobo</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Fernanda Caramella-Pereira</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Luigi Marchionni</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Charles G. Drake</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Tamara Lotan</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Angelo M. De Marzo</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Justin Hwang</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Emmanuel S. Antonarakis</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="773" ind1="0" ind2="8"><subfield code="i">In</subfield><subfield code="t">npj Genomic Medicine</subfield><subfield code="d">Nature Portfolio, 2016</subfield><subfield code="g">9(2024), 1, Seite 9</subfield><subfield code="w">(DE-627)820061727</subfield><subfield code="w">(DE-600)2813848-X</subfield><subfield code="x">20567944</subfield><subfield code="7">nnns</subfield></datafield><datafield tag="773" ind1="1" ind2="8"><subfield code="g">volume:9</subfield><subfield code="g">year:2024</subfield><subfield code="g">number:1</subfield><subfield code="g">pages:9</subfield></datafield><datafield tag="856" ind1="4" ind2="0"><subfield code="u">https://doi.org/10.1038/s41525-024-00392-1</subfield><subfield code="z">kostenfrei</subfield></datafield><datafield tag="856" ind1="4" ind2="0"><subfield code="u">https://doaj.org/article/a63fc47e643a46939677c01b1b4e10df</subfield><subfield code="z">kostenfrei</subfield></datafield><datafield tag="856" ind1="4" ind2="0"><subfield code="u">https://doi.org/10.1038/s41525-024-00392-1</subfield><subfield code="z">kostenfrei</subfield></datafield><datafield tag="856" ind1="4" ind2="2"><subfield code="u">https://doaj.org/toc/2056-7944</subfield><subfield code="y">Journal toc</subfield><subfield code="z">kostenfrei</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_USEFLAG_A</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SYSFLAG_A</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_DOAJ</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_20</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_22</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_23</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_24</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_39</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_40</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_60</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_62</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_63</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_65</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_69</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_73</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_74</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_95</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_105</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_110</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_151</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_161</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_170</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_206</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_213</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_230</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_285</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_293</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_602</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2014</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4012</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4037</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4112</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4125</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4126</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4249</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4305</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4306</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4307</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4313</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4322</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4323</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4324</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4325</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4338</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4367</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4700</subfield></datafield><datafield tag="951" ind1=" " ind2=" "><subfield code="a">AR</subfield></datafield><datafield tag="952" ind1=" " ind2=" "><subfield code="d">9</subfield><subfield code="j">2024</subfield><subfield code="e">1</subfield><subfield code="h">9</subfield></datafield></record></collection>
|
| callnumber-first |
Q - Science |
| author |
Hannah E. Bergom |
| spellingShingle |
Hannah E. Bergom misc QH426-470 misc Medicine misc R misc Genetics Divergent immune microenvironments in two tumor nodules from a patient with mismatch repair-deficient prostate cancer |
| authorStr |
Hannah E. Bergom |
| ppnlink_with_tag_str_mv |
@@773@@(DE-627)820061727 |
| format |
electronic Article |
| delete_txt_mv |
keep |
| author_role |
aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut |
| collection |
DOAJ |
| remote_str |
true |
| callnumber-label |
QH426-470 |
| illustrated |
Not Illustrated |
| issn |
20567944 |
| topic_title |
QH426-470 Divergent immune microenvironments in two tumor nodules from a patient with mismatch repair-deficient prostate cancer |
| topic |
misc QH426-470 misc Medicine misc R misc Genetics |
| topic_unstemmed |
misc QH426-470 misc Medicine misc R misc Genetics |
| topic_browse |
misc QH426-470 misc Medicine misc R misc Genetics |
| format_facet |
Elektronische Aufsätze Aufsätze Elektronische Ressource |
| format_main_str_mv |
Text Zeitschrift/Artikel |
| carriertype_str_mv |
cr |
| hierarchy_parent_title |
npj Genomic Medicine |
| hierarchy_parent_id |
820061727 |
| hierarchy_top_title |
npj Genomic Medicine |
| isfreeaccess_txt |
true |
| familylinks_str_mv |
(DE-627)820061727 (DE-600)2813848-X |
| title |
Divergent immune microenvironments in two tumor nodules from a patient with mismatch repair-deficient prostate cancer |
| ctrlnum |
(DE-627)DOAJ092212646 (DE-599)DOAJa63fc47e643a46939677c01b1b4e10df |
| title_full |
Divergent immune microenvironments in two tumor nodules from a patient with mismatch repair-deficient prostate cancer |
| author_sort |
Hannah E. Bergom |
| journal |
npj Genomic Medicine |
| journalStr |
npj Genomic Medicine |
| callnumber-first-code |
Q |
| lang_code |
eng |
| isOA_bool |
true |
| recordtype |
marc |
| publishDateSort |
2024 |
| contenttype_str_mv |
txt |
| container_start_page |
9 |
| author_browse |
Hannah E. Bergom Laura A. Sena Abderrahman Day Benjamin Miller Carly D. Miller John R. Lozada Nicholas Zorko Jinhua Wang Eugene Shenderov Francisco Pereira Lobo Fernanda Caramella-Pereira Luigi Marchionni Charles G. Drake Tamara Lotan Angelo M. De Marzo Justin Hwang Emmanuel S. Antonarakis |
| container_volume |
9 |
| class |
QH426-470 |
| format_se |
Elektronische Aufsätze |
| author-letter |
Hannah E. Bergom |
| doi_str_mv |
10.1038/s41525-024-00392-1 |
| author2-role |
verfasserin |
| title_sort |
divergent immune microenvironments in two tumor nodules from a patient with mismatch repair-deficient prostate cancer |
| callnumber |
QH426-470 |
| title_auth |
Divergent immune microenvironments in two tumor nodules from a patient with mismatch repair-deficient prostate cancer |
| abstract |
Abstract Patients with prostate cancer (PC) generally do not respond favorably to immune checkpoint inhibitors, which may be due to a low abundance of tumor-infiltrating lymphocytes even when mutational load is high. Here, we identified a patient who presented with high-grade primary prostate cancer with two adjacent tumor nodules. While both nodules were mismatch repair-deficient (MMRd), exhibited pathogenic MSH2 and MSH6 alterations, had a high tumor mutational burden (TMB), and demonstrated high microsatellite instability (MSI), they had markedly distinct immune phenotypes. The first displayed a dense infiltrate of lymphocytes (“hot nodule”), while the second displayed significantly fewer infiltrating lymphocytes (“cold nodule”). Whole-exome DNA analysis found that both nodules shared many identical mutations, indicating that they were derived from a single clone. However, the cold nodule appeared to be sub-clonal relative to the hot nodule, suggesting divergent evolution of the cold nodule from the hot nodule. Whole-transcriptome RNA analysis found that the cold nodule demonstrated lower expression of genes related to antigen presentation (HLA) and, paradoxically, classical tumor immune tolerance markers such as PD-L1 (CD274) and CTLA-4. Immune cell deconvolution suggested that the hot nodule was enriched not only in CD8+ and CD4 + T lymphocytes, but also in M1 macrophages, activated NK cells, and γδ T cells compared to the cold nodule. This case highlights that MMRd/TMB-high PC can evolve to minimize an anti-tumor immune response, and nominates downregulation of antigen presentation machinery (HLA loss) as a potential mechanism of adaptive immune evasion in PC. |
| abstractGer |
Abstract Patients with prostate cancer (PC) generally do not respond favorably to immune checkpoint inhibitors, which may be due to a low abundance of tumor-infiltrating lymphocytes even when mutational load is high. Here, we identified a patient who presented with high-grade primary prostate cancer with two adjacent tumor nodules. While both nodules were mismatch repair-deficient (MMRd), exhibited pathogenic MSH2 and MSH6 alterations, had a high tumor mutational burden (TMB), and demonstrated high microsatellite instability (MSI), they had markedly distinct immune phenotypes. The first displayed a dense infiltrate of lymphocytes (“hot nodule”), while the second displayed significantly fewer infiltrating lymphocytes (“cold nodule”). Whole-exome DNA analysis found that both nodules shared many identical mutations, indicating that they were derived from a single clone. However, the cold nodule appeared to be sub-clonal relative to the hot nodule, suggesting divergent evolution of the cold nodule from the hot nodule. Whole-transcriptome RNA analysis found that the cold nodule demonstrated lower expression of genes related to antigen presentation (HLA) and, paradoxically, classical tumor immune tolerance markers such as PD-L1 (CD274) and CTLA-4. Immune cell deconvolution suggested that the hot nodule was enriched not only in CD8+ and CD4 + T lymphocytes, but also in M1 macrophages, activated NK cells, and γδ T cells compared to the cold nodule. This case highlights that MMRd/TMB-high PC can evolve to minimize an anti-tumor immune response, and nominates downregulation of antigen presentation machinery (HLA loss) as a potential mechanism of adaptive immune evasion in PC. |
| abstract_unstemmed |
Abstract Patients with prostate cancer (PC) generally do not respond favorably to immune checkpoint inhibitors, which may be due to a low abundance of tumor-infiltrating lymphocytes even when mutational load is high. Here, we identified a patient who presented with high-grade primary prostate cancer with two adjacent tumor nodules. While both nodules were mismatch repair-deficient (MMRd), exhibited pathogenic MSH2 and MSH6 alterations, had a high tumor mutational burden (TMB), and demonstrated high microsatellite instability (MSI), they had markedly distinct immune phenotypes. The first displayed a dense infiltrate of lymphocytes (“hot nodule”), while the second displayed significantly fewer infiltrating lymphocytes (“cold nodule”). Whole-exome DNA analysis found that both nodules shared many identical mutations, indicating that they were derived from a single clone. However, the cold nodule appeared to be sub-clonal relative to the hot nodule, suggesting divergent evolution of the cold nodule from the hot nodule. Whole-transcriptome RNA analysis found that the cold nodule demonstrated lower expression of genes related to antigen presentation (HLA) and, paradoxically, classical tumor immune tolerance markers such as PD-L1 (CD274) and CTLA-4. Immune cell deconvolution suggested that the hot nodule was enriched not only in CD8+ and CD4 + T lymphocytes, but also in M1 macrophages, activated NK cells, and γδ T cells compared to the cold nodule. This case highlights that MMRd/TMB-high PC can evolve to minimize an anti-tumor immune response, and nominates downregulation of antigen presentation machinery (HLA loss) as a potential mechanism of adaptive immune evasion in PC. |
| collection_details |
GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 |
| container_issue |
1 |
| title_short |
Divergent immune microenvironments in two tumor nodules from a patient with mismatch repair-deficient prostate cancer |
| url |
https://doi.org/10.1038/s41525-024-00392-1 https://doaj.org/article/a63fc47e643a46939677c01b1b4e10df https://doaj.org/toc/2056-7944 |
| remote_bool |
true |
| author2 |
Laura A. Sena Abderrahman Day Benjamin Miller Carly D. Miller John R. Lozada Nicholas Zorko Jinhua Wang Eugene Shenderov Francisco Pereira Lobo Fernanda Caramella-Pereira Luigi Marchionni Charles G. Drake Tamara Lotan Angelo M. De Marzo Justin Hwang Emmanuel S. Antonarakis |
| author2Str |
Laura A. Sena Abderrahman Day Benjamin Miller Carly D. Miller John R. Lozada Nicholas Zorko Jinhua Wang Eugene Shenderov Francisco Pereira Lobo Fernanda Caramella-Pereira Luigi Marchionni Charles G. Drake Tamara Lotan Angelo M. De Marzo Justin Hwang Emmanuel S. Antonarakis |
| ppnlink |
820061727 |
| callnumber-subject |
QH - Natural History and Biology |
| mediatype_str_mv |
c |
| isOA_txt |
true |
| hochschulschrift_bool |
false |
| doi_str |
10.1038/s41525-024-00392-1 |
| callnumber-a |
QH426-470 |
| up_date |
2024-07-04T00:30:03.136Z |
| _version_ |
1803606297817382912 |
| fullrecord_marcxml |
<?xml version="1.0" encoding="UTF-8"?><collection xmlns="http://www.loc.gov/MARC21/slim"><record><leader>01000caa a22002652 4500</leader><controlfield tag="001">DOAJ092212646</controlfield><controlfield tag="003">DE-627</controlfield><controlfield tag="005">20240414094250.0</controlfield><controlfield tag="007">cr uuu---uuuuu</controlfield><controlfield tag="008">240412s2024 xx |||||o 00| ||eng c</controlfield><datafield tag="024" ind1="7" ind2=" "><subfield code="a">10.1038/s41525-024-00392-1</subfield><subfield code="2">doi</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-627)DOAJ092212646</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-599)DOAJa63fc47e643a46939677c01b1b4e10df</subfield></datafield><datafield tag="040" ind1=" " ind2=" "><subfield code="a">DE-627</subfield><subfield code="b">ger</subfield><subfield code="c">DE-627</subfield><subfield code="e">rakwb</subfield></datafield><datafield tag="041" ind1=" " ind2=" "><subfield code="a">eng</subfield></datafield><datafield tag="050" ind1=" " ind2="0"><subfield code="a">QH426-470</subfield></datafield><datafield tag="100" ind1="0" ind2=" "><subfield code="a">Hannah E. Bergom</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">Divergent immune microenvironments in two tumor nodules from a patient with mismatch repair-deficient prostate cancer</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">2024</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="a">Text</subfield><subfield code="b">txt</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="a">Computermedien</subfield><subfield code="b">c</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="a">Online-Ressource</subfield><subfield code="b">cr</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Abstract Patients with prostate cancer (PC) generally do not respond favorably to immune checkpoint inhibitors, which may be due to a low abundance of tumor-infiltrating lymphocytes even when mutational load is high. Here, we identified a patient who presented with high-grade primary prostate cancer with two adjacent tumor nodules. While both nodules were mismatch repair-deficient (MMRd), exhibited pathogenic MSH2 and MSH6 alterations, had a high tumor mutational burden (TMB), and demonstrated high microsatellite instability (MSI), they had markedly distinct immune phenotypes. The first displayed a dense infiltrate of lymphocytes (“hot nodule”), while the second displayed significantly fewer infiltrating lymphocytes (“cold nodule”). Whole-exome DNA analysis found that both nodules shared many identical mutations, indicating that they were derived from a single clone. However, the cold nodule appeared to be sub-clonal relative to the hot nodule, suggesting divergent evolution of the cold nodule from the hot nodule. Whole-transcriptome RNA analysis found that the cold nodule demonstrated lower expression of genes related to antigen presentation (HLA) and, paradoxically, classical tumor immune tolerance markers such as PD-L1 (CD274) and CTLA-4. Immune cell deconvolution suggested that the hot nodule was enriched not only in CD8+ and CD4 + T lymphocytes, but also in M1 macrophages, activated NK cells, and γδ T cells compared to the cold nodule. This case highlights that MMRd/TMB-high PC can evolve to minimize an anti-tumor immune response, and nominates downregulation of antigen presentation machinery (HLA loss) as a potential mechanism of adaptive immune evasion in PC.</subfield></datafield><datafield tag="653" ind1=" " ind2="0"><subfield code="a">Medicine</subfield></datafield><datafield tag="653" ind1=" " ind2="0"><subfield code="a">R</subfield></datafield><datafield tag="653" ind1=" " ind2="0"><subfield code="a">Genetics</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Laura A. Sena</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Abderrahman Day</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Benjamin Miller</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Carly D. Miller</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">John R. Lozada</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Nicholas Zorko</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Jinhua Wang</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Eugene Shenderov</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Francisco Pereira Lobo</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Fernanda Caramella-Pereira</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Luigi Marchionni</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Charles G. Drake</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Tamara Lotan</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Angelo M. De Marzo</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Justin Hwang</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Emmanuel S. Antonarakis</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="773" ind1="0" ind2="8"><subfield code="i">In</subfield><subfield code="t">npj Genomic Medicine</subfield><subfield code="d">Nature Portfolio, 2016</subfield><subfield code="g">9(2024), 1, Seite 9</subfield><subfield code="w">(DE-627)820061727</subfield><subfield code="w">(DE-600)2813848-X</subfield><subfield code="x">20567944</subfield><subfield code="7">nnns</subfield></datafield><datafield tag="773" ind1="1" ind2="8"><subfield code="g">volume:9</subfield><subfield code="g">year:2024</subfield><subfield code="g">number:1</subfield><subfield code="g">pages:9</subfield></datafield><datafield tag="856" ind1="4" ind2="0"><subfield code="u">https://doi.org/10.1038/s41525-024-00392-1</subfield><subfield code="z">kostenfrei</subfield></datafield><datafield tag="856" ind1="4" ind2="0"><subfield code="u">https://doaj.org/article/a63fc47e643a46939677c01b1b4e10df</subfield><subfield code="z">kostenfrei</subfield></datafield><datafield tag="856" ind1="4" ind2="0"><subfield code="u">https://doi.org/10.1038/s41525-024-00392-1</subfield><subfield code="z">kostenfrei</subfield></datafield><datafield tag="856" ind1="4" ind2="2"><subfield code="u">https://doaj.org/toc/2056-7944</subfield><subfield code="y">Journal toc</subfield><subfield code="z">kostenfrei</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_USEFLAG_A</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SYSFLAG_A</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_DOAJ</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_20</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_22</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_23</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_24</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_39</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_40</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_60</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_62</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_63</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_65</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_69</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_73</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_74</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_95</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_105</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_110</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_151</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_161</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_170</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_206</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_213</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_230</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_285</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_293</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_602</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2014</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4012</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4037</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4112</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4125</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4126</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4249</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4305</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4306</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4307</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4313</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4322</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4323</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4324</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4325</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4338</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4367</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4700</subfield></datafield><datafield tag="951" ind1=" " ind2=" "><subfield code="a">AR</subfield></datafield><datafield tag="952" ind1=" " ind2=" "><subfield code="d">9</subfield><subfield code="j">2024</subfield><subfield code="e">1</subfield><subfield code="h">9</subfield></datafield></record></collection>
|
| score |
7.4012585 |