Interspatial Distribution of Tumor and Immune Cells in Correlation with PD-L1 in Molecular Subtypes of Gastric Cancers

(1) Background: EBV-positive and mismatch repair-deficient (MMRd) gastric cancers (GCs) show higher levels of tumor-infiltrating lymphocytes (TILs) and PD-L1 expression and thus a more profound response to immunotherapy. However, the majority of GCs are EBV-negative (EBV−) and MMR proficient (MMRp)....
Ausführliche Beschreibung

Gespeichert in:

Autor*in:	Bastian Dislich [verfasserIn] Kirsten D. Mertz [verfasserIn] Beat Gloor [verfasserIn] Rupert Langer [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2022

Schlagwörter:	gastric cancer PD-L1 TIL EBV MMR MSI

Übergeordnetes Werk:	In: Cancers - MDPI AG, 2010, 14(2022), 7, p 1736
Übergeordnetes Werk:	volume:14 ; year:2022 ; number:7, p 1736

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.3390/cancers14071736

Katalog-ID:	DOAJ05924657X

Internformat


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520			\|a (1) Background: EBV-positive and mismatch repair-deficient (MMRd) gastric cancers (GCs) show higher levels of tumor-infiltrating lymphocytes (TILs) and PD-L1 expression and thus a more profound response to immunotherapy. However, the majority of GCs are EBV-negative (EBV−) and MMR proficient (MMRp). We analyzed PD-L1 expression and TILs in EBV-MMRpGCs in comparison to EBV-positive (EBV+) and MMRdGCs to identify an immunogenic phenotype susceptible to immunotherapy. (2) Methods: A next-generation tissue microarray of 409 primary resected GCs was analyzed by Epstein-Barr encoding region (EBER) in situ hybridization for MSH1, PMS2, MSH2, MSH6, PD-L1, and CD8 immunohistochemistry. PD-L1 positivity was defined as a combined positive score (CPS) of ≥1. CD8+ TILs and their proximity to cancer cells were digitally analyzed on the HALO™ image analysis platform. (3) Results: Eleven cases were EBV+, 49 cases MMRd, and 349 cases EBV-MMRpGCs. The highest rate of PD-L1 positivity was seen in EBV+GCs, followed by MMRdGCs and EBV-MMRpGCs (81.8%, 73.5%, and 27.8%, respectively). EBV+ and MMRdGCs also demonstrated increased numbers and proximity of CD8+ TILs to tumor cells compared to EBV-MMRpGCs (<i<p</i< < 0.001 each). PD-L1 status positively correlated with the total numbers of CD8+ TILs and their proximity to tumor cells in all subtypes, including EBV-MMRpGCs (<i<p</i< < 0.001 each). A total of 28.4% of EBV-MMRpGCs showed high CD8+ TILs independent of PD-L1. (4) Conclusions: PD-L1 and CD8 immunohistochemistry, supplemented by digital image analysis, may identify EBV-MMRpGCs with high immunoreactivity indices, indicating susceptibility to immunotherapy.
650		4	\|a gastric cancer
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author_variant	b d bd k d m kdm b g bg r l rl
matchkey_str	article:20726694:2022----::nesailitiuinfuoadmueelicreainihd1noeu
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allfields	10.3390/cancers14071736 doi (DE-627)DOAJ05924657X (DE-599)DOAJ106228609a3a4cb4900e33f8fcde2980 DE-627 ger DE-627 rakwb eng RC254-282 Bastian Dislich verfasserin aut Interspatial Distribution of Tumor and Immune Cells in Correlation with PD-L1 in Molecular Subtypes of Gastric Cancers 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier (1) Background: EBV-positive and mismatch repair-deficient (MMRd) gastric cancers (GCs) show higher levels of tumor-infiltrating lymphocytes (TILs) and PD-L1 expression and thus a more profound response to immunotherapy. However, the majority of GCs are EBV-negative (EBV−) and MMR proficient (MMRp). We analyzed PD-L1 expression and TILs in EBV-MMRpGCs in comparison to EBV-positive (EBV+) and MMRdGCs to identify an immunogenic phenotype susceptible to immunotherapy. (2) Methods: A next-generation tissue microarray of 409 primary resected GCs was analyzed by Epstein-Barr encoding region (EBER) in situ hybridization for MSH1, PMS2, MSH2, MSH6, PD-L1, and CD8 immunohistochemistry. PD-L1 positivity was defined as a combined positive score (CPS) of ≥1. CD8+ TILs and their proximity to cancer cells were digitally analyzed on the HALO™ image analysis platform. (3) Results: Eleven cases were EBV+, 49 cases MMRd, and 349 cases EBV-MMRpGCs. The highest rate of PD-L1 positivity was seen in EBV+GCs, followed by MMRdGCs and EBV-MMRpGCs (81.8%, 73.5%, and 27.8%, respectively). EBV+ and MMRdGCs also demonstrated increased numbers and proximity of CD8+ TILs to tumor cells compared to EBV-MMRpGCs (<i<p</i< < 0.001 each). PD-L1 status positively correlated with the total numbers of CD8+ TILs and their proximity to tumor cells in all subtypes, including EBV-MMRpGCs (<i<p</i< < 0.001 each). A total of 28.4% of EBV-MMRpGCs showed high CD8+ TILs independent of PD-L1. (4) Conclusions: PD-L1 and CD8 immunohistochemistry, supplemented by digital image analysis, may identify EBV-MMRpGCs with high immunoreactivity indices, indicating susceptibility to immunotherapy. gastric cancer PD-L1 TIL EBV MMR MSI Neoplasms. Tumors. Oncology. Including cancer and carcinogens Kirsten D. Mertz verfasserin aut Beat Gloor verfasserin aut Rupert Langer verfasserin aut In Cancers MDPI AG, 2010 14(2022), 7, p 1736 (DE-627)614095670 (DE-600)2527080-1 20726694 nnns volume:14 year:2022 number:7, p 1736 https://doi.org/10.3390/cancers14071736 kostenfrei https://doaj.org/article/106228609a3a4cb4900e33f8fcde2980 kostenfrei https://www.mdpi.com/2072-6694/14/7/1736 kostenfrei https://doaj.org/toc/2072-6694 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_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 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 14 2022 7, p 1736
spelling	10.3390/cancers14071736 doi (DE-627)DOAJ05924657X (DE-599)DOAJ106228609a3a4cb4900e33f8fcde2980 DE-627 ger DE-627 rakwb eng RC254-282 Bastian Dislich verfasserin aut Interspatial Distribution of Tumor and Immune Cells in Correlation with PD-L1 in Molecular Subtypes of Gastric Cancers 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier (1) Background: EBV-positive and mismatch repair-deficient (MMRd) gastric cancers (GCs) show higher levels of tumor-infiltrating lymphocytes (TILs) and PD-L1 expression and thus a more profound response to immunotherapy. However, the majority of GCs are EBV-negative (EBV−) and MMR proficient (MMRp). We analyzed PD-L1 expression and TILs in EBV-MMRpGCs in comparison to EBV-positive (EBV+) and MMRdGCs to identify an immunogenic phenotype susceptible to immunotherapy. (2) Methods: A next-generation tissue microarray of 409 primary resected GCs was analyzed by Epstein-Barr encoding region (EBER) in situ hybridization for MSH1, PMS2, MSH2, MSH6, PD-L1, and CD8 immunohistochemistry. PD-L1 positivity was defined as a combined positive score (CPS) of ≥1. CD8+ TILs and their proximity to cancer cells were digitally analyzed on the HALO™ image analysis platform. (3) Results: Eleven cases were EBV+, 49 cases MMRd, and 349 cases EBV-MMRpGCs. The highest rate of PD-L1 positivity was seen in EBV+GCs, followed by MMRdGCs and EBV-MMRpGCs (81.8%, 73.5%, and 27.8%, respectively). EBV+ and MMRdGCs also demonstrated increased numbers and proximity of CD8+ TILs to tumor cells compared to EBV-MMRpGCs (<i<p</i< < 0.001 each). PD-L1 status positively correlated with the total numbers of CD8+ TILs and their proximity to tumor cells in all subtypes, including EBV-MMRpGCs (<i<p</i< < 0.001 each). A total of 28.4% of EBV-MMRpGCs showed high CD8+ TILs independent of PD-L1. (4) Conclusions: PD-L1 and CD8 immunohistochemistry, supplemented by digital image analysis, may identify EBV-MMRpGCs with high immunoreactivity indices, indicating susceptibility to immunotherapy. gastric cancer PD-L1 TIL EBV MMR MSI Neoplasms. Tumors. Oncology. Including cancer and carcinogens Kirsten D. Mertz verfasserin aut Beat Gloor verfasserin aut Rupert Langer verfasserin aut In Cancers MDPI AG, 2010 14(2022), 7, p 1736 (DE-627)614095670 (DE-600)2527080-1 20726694 nnns volume:14 year:2022 number:7, p 1736 https://doi.org/10.3390/cancers14071736 kostenfrei https://doaj.org/article/106228609a3a4cb4900e33f8fcde2980 kostenfrei https://www.mdpi.com/2072-6694/14/7/1736 kostenfrei https://doaj.org/toc/2072-6694 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_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 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 14 2022 7, p 1736
allfields_unstemmed	10.3390/cancers14071736 doi (DE-627)DOAJ05924657X (DE-599)DOAJ106228609a3a4cb4900e33f8fcde2980 DE-627 ger DE-627 rakwb eng RC254-282 Bastian Dislich verfasserin aut Interspatial Distribution of Tumor and Immune Cells in Correlation with PD-L1 in Molecular Subtypes of Gastric Cancers 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier (1) Background: EBV-positive and mismatch repair-deficient (MMRd) gastric cancers (GCs) show higher levels of tumor-infiltrating lymphocytes (TILs) and PD-L1 expression and thus a more profound response to immunotherapy. However, the majority of GCs are EBV-negative (EBV−) and MMR proficient (MMRp). We analyzed PD-L1 expression and TILs in EBV-MMRpGCs in comparison to EBV-positive (EBV+) and MMRdGCs to identify an immunogenic phenotype susceptible to immunotherapy. (2) Methods: A next-generation tissue microarray of 409 primary resected GCs was analyzed by Epstein-Barr encoding region (EBER) in situ hybridization for MSH1, PMS2, MSH2, MSH6, PD-L1, and CD8 immunohistochemistry. PD-L1 positivity was defined as a combined positive score (CPS) of ≥1. CD8+ TILs and their proximity to cancer cells were digitally analyzed on the HALO™ image analysis platform. (3) Results: Eleven cases were EBV+, 49 cases MMRd, and 349 cases EBV-MMRpGCs. The highest rate of PD-L1 positivity was seen in EBV+GCs, followed by MMRdGCs and EBV-MMRpGCs (81.8%, 73.5%, and 27.8%, respectively). EBV+ and MMRdGCs also demonstrated increased numbers and proximity of CD8+ TILs to tumor cells compared to EBV-MMRpGCs (<i<p</i< < 0.001 each). PD-L1 status positively correlated with the total numbers of CD8+ TILs and their proximity to tumor cells in all subtypes, including EBV-MMRpGCs (<i<p</i< < 0.001 each). A total of 28.4% of EBV-MMRpGCs showed high CD8+ TILs independent of PD-L1. (4) Conclusions: PD-L1 and CD8 immunohistochemistry, supplemented by digital image analysis, may identify EBV-MMRpGCs with high immunoreactivity indices, indicating susceptibility to immunotherapy. gastric cancer PD-L1 TIL EBV MMR MSI Neoplasms. Tumors. Oncology. Including cancer and carcinogens Kirsten D. Mertz verfasserin aut Beat Gloor verfasserin aut Rupert Langer verfasserin aut In Cancers MDPI AG, 2010 14(2022), 7, p 1736 (DE-627)614095670 (DE-600)2527080-1 20726694 nnns volume:14 year:2022 number:7, p 1736 https://doi.org/10.3390/cancers14071736 kostenfrei https://doaj.org/article/106228609a3a4cb4900e33f8fcde2980 kostenfrei https://www.mdpi.com/2072-6694/14/7/1736 kostenfrei https://doaj.org/toc/2072-6694 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_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 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 14 2022 7, p 1736
allfieldsGer	10.3390/cancers14071736 doi (DE-627)DOAJ05924657X (DE-599)DOAJ106228609a3a4cb4900e33f8fcde2980 DE-627 ger DE-627 rakwb eng RC254-282 Bastian Dislich verfasserin aut Interspatial Distribution of Tumor and Immune Cells in Correlation with PD-L1 in Molecular Subtypes of Gastric Cancers 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier (1) Background: EBV-positive and mismatch repair-deficient (MMRd) gastric cancers (GCs) show higher levels of tumor-infiltrating lymphocytes (TILs) and PD-L1 expression and thus a more profound response to immunotherapy. However, the majority of GCs are EBV-negative (EBV−) and MMR proficient (MMRp). We analyzed PD-L1 expression and TILs in EBV-MMRpGCs in comparison to EBV-positive (EBV+) and MMRdGCs to identify an immunogenic phenotype susceptible to immunotherapy. (2) Methods: A next-generation tissue microarray of 409 primary resected GCs was analyzed by Epstein-Barr encoding region (EBER) in situ hybridization for MSH1, PMS2, MSH2, MSH6, PD-L1, and CD8 immunohistochemistry. PD-L1 positivity was defined as a combined positive score (CPS) of ≥1. CD8+ TILs and their proximity to cancer cells were digitally analyzed on the HALO™ image analysis platform. (3) Results: Eleven cases were EBV+, 49 cases MMRd, and 349 cases EBV-MMRpGCs. The highest rate of PD-L1 positivity was seen in EBV+GCs, followed by MMRdGCs and EBV-MMRpGCs (81.8%, 73.5%, and 27.8%, respectively). EBV+ and MMRdGCs also demonstrated increased numbers and proximity of CD8+ TILs to tumor cells compared to EBV-MMRpGCs (<i<p</i< < 0.001 each). PD-L1 status positively correlated with the total numbers of CD8+ TILs and their proximity to tumor cells in all subtypes, including EBV-MMRpGCs (<i<p</i< < 0.001 each). A total of 28.4% of EBV-MMRpGCs showed high CD8+ TILs independent of PD-L1. (4) Conclusions: PD-L1 and CD8 immunohistochemistry, supplemented by digital image analysis, may identify EBV-MMRpGCs with high immunoreactivity indices, indicating susceptibility to immunotherapy. gastric cancer PD-L1 TIL EBV MMR MSI Neoplasms. Tumors. Oncology. Including cancer and carcinogens Kirsten D. Mertz verfasserin aut Beat Gloor verfasserin aut Rupert Langer verfasserin aut In Cancers MDPI AG, 2010 14(2022), 7, p 1736 (DE-627)614095670 (DE-600)2527080-1 20726694 nnns volume:14 year:2022 number:7, p 1736 https://doi.org/10.3390/cancers14071736 kostenfrei https://doaj.org/article/106228609a3a4cb4900e33f8fcde2980 kostenfrei https://www.mdpi.com/2072-6694/14/7/1736 kostenfrei https://doaj.org/toc/2072-6694 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_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 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 14 2022 7, p 1736
allfieldsSound	10.3390/cancers14071736 doi (DE-627)DOAJ05924657X (DE-599)DOAJ106228609a3a4cb4900e33f8fcde2980 DE-627 ger DE-627 rakwb eng RC254-282 Bastian Dislich verfasserin aut Interspatial Distribution of Tumor and Immune Cells in Correlation with PD-L1 in Molecular Subtypes of Gastric Cancers 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier (1) Background: EBV-positive and mismatch repair-deficient (MMRd) gastric cancers (GCs) show higher levels of tumor-infiltrating lymphocytes (TILs) and PD-L1 expression and thus a more profound response to immunotherapy. However, the majority of GCs are EBV-negative (EBV−) and MMR proficient (MMRp). We analyzed PD-L1 expression and TILs in EBV-MMRpGCs in comparison to EBV-positive (EBV+) and MMRdGCs to identify an immunogenic phenotype susceptible to immunotherapy. (2) Methods: A next-generation tissue microarray of 409 primary resected GCs was analyzed by Epstein-Barr encoding region (EBER) in situ hybridization for MSH1, PMS2, MSH2, MSH6, PD-L1, and CD8 immunohistochemistry. PD-L1 positivity was defined as a combined positive score (CPS) of ≥1. CD8+ TILs and their proximity to cancer cells were digitally analyzed on the HALO™ image analysis platform. (3) Results: Eleven cases were EBV+, 49 cases MMRd, and 349 cases EBV-MMRpGCs. The highest rate of PD-L1 positivity was seen in EBV+GCs, followed by MMRdGCs and EBV-MMRpGCs (81.8%, 73.5%, and 27.8%, respectively). EBV+ and MMRdGCs also demonstrated increased numbers and proximity of CD8+ TILs to tumor cells compared to EBV-MMRpGCs (<i<p</i< < 0.001 each). PD-L1 status positively correlated with the total numbers of CD8+ TILs and their proximity to tumor cells in all subtypes, including EBV-MMRpGCs (<i<p</i< < 0.001 each). A total of 28.4% of EBV-MMRpGCs showed high CD8+ TILs independent of PD-L1. (4) Conclusions: PD-L1 and CD8 immunohistochemistry, supplemented by digital image analysis, may identify EBV-MMRpGCs with high immunoreactivity indices, indicating susceptibility to immunotherapy. gastric cancer PD-L1 TIL EBV MMR MSI Neoplasms. Tumors. Oncology. Including cancer and carcinogens Kirsten D. Mertz verfasserin aut Beat Gloor verfasserin aut Rupert Langer verfasserin aut In Cancers MDPI AG, 2010 14(2022), 7, p 1736 (DE-627)614095670 (DE-600)2527080-1 20726694 nnns volume:14 year:2022 number:7, p 1736 https://doi.org/10.3390/cancers14071736 kostenfrei https://doaj.org/article/106228609a3a4cb4900e33f8fcde2980 kostenfrei https://www.mdpi.com/2072-6694/14/7/1736 kostenfrei https://doaj.org/toc/2072-6694 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_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 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 14 2022 7, p 1736
language	English
source	In Cancers 14(2022), 7, p 1736 volume:14 year:2022 number:7, p 1736
sourceStr	In Cancers 14(2022), 7, p 1736 volume:14 year:2022 number:7, p 1736
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	gastric cancer PD-L1 TIL EBV MMR MSI Neoplasms. Tumors. Oncology. Including cancer and carcinogens
isfreeaccess_bool	true
container_title	Cancers
authorswithroles_txt_mv	Bastian Dislich @@aut@@ Kirsten D. Mertz @@aut@@ Beat Gloor @@aut@@ Rupert Langer @@aut@@
publishDateDaySort_date	2022-01-01T00:00:00Z
hierarchy_top_id	614095670
id	DOAJ05924657X
language_de	englisch
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callnumber-first	R - Medicine
author	Bastian Dislich
spellingShingle	Bastian Dislich misc RC254-282 misc gastric cancer misc PD-L1 misc TIL misc EBV misc MMR misc MSI misc Neoplasms. Tumors. Oncology. Including cancer and carcinogens Interspatial Distribution of Tumor and Immune Cells in Correlation with PD-L1 in Molecular Subtypes of Gastric Cancers
authorStr	Bastian Dislich
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topic_title	RC254-282 Interspatial Distribution of Tumor and Immune Cells in Correlation with PD-L1 in Molecular Subtypes of Gastric Cancers gastric cancer PD-L1 TIL EBV MMR MSI
topic	misc RC254-282 misc gastric cancer misc PD-L1 misc TIL misc EBV misc MMR misc MSI misc Neoplasms. Tumors. Oncology. Including cancer and carcinogens
topic_unstemmed	misc RC254-282 misc gastric cancer misc PD-L1 misc TIL misc EBV misc MMR misc MSI misc Neoplasms. Tumors. Oncology. Including cancer and carcinogens
topic_browse	misc RC254-282 misc gastric cancer misc PD-L1 misc TIL misc EBV misc MMR misc MSI misc Neoplasms. Tumors. Oncology. Including cancer and carcinogens
format_facet	Elektronische Aufsätze Aufsätze Elektronische Ressource
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hierarchy_parent_title	Cancers
hierarchy_parent_id	614095670
hierarchy_top_title	Cancers
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title	Interspatial Distribution of Tumor and Immune Cells in Correlation with PD-L1 in Molecular Subtypes of Gastric Cancers
ctrlnum	(DE-627)DOAJ05924657X (DE-599)DOAJ106228609a3a4cb4900e33f8fcde2980
title_full	Interspatial Distribution of Tumor and Immune Cells in Correlation with PD-L1 in Molecular Subtypes of Gastric Cancers
author_sort	Bastian Dislich
journal	Cancers
journalStr	Cancers
callnumber-first-code	R
lang_code	eng
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publishDateSort	2022
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author_browse	Bastian Dislich Kirsten D. Mertz Beat Gloor Rupert Langer
container_volume	14
class	RC254-282
format_se	Elektronische Aufsätze
author-letter	Bastian Dislich
doi_str_mv	10.3390/cancers14071736
author2-role	verfasserin
title_sort	interspatial distribution of tumor and immune cells in correlation with pd-l1 in molecular subtypes of gastric cancers
callnumber	RC254-282
title_auth	Interspatial Distribution of Tumor and Immune Cells in Correlation with PD-L1 in Molecular Subtypes of Gastric Cancers
abstract	(1) Background: EBV-positive and mismatch repair-deficient (MMRd) gastric cancers (GCs) show higher levels of tumor-infiltrating lymphocytes (TILs) and PD-L1 expression and thus a more profound response to immunotherapy. However, the majority of GCs are EBV-negative (EBV−) and MMR proficient (MMRp). We analyzed PD-L1 expression and TILs in EBV-MMRpGCs in comparison to EBV-positive (EBV+) and MMRdGCs to identify an immunogenic phenotype susceptible to immunotherapy. (2) Methods: A next-generation tissue microarray of 409 primary resected GCs was analyzed by Epstein-Barr encoding region (EBER) in situ hybridization for MSH1, PMS2, MSH2, MSH6, PD-L1, and CD8 immunohistochemistry. PD-L1 positivity was defined as a combined positive score (CPS) of ≥1. CD8+ TILs and their proximity to cancer cells were digitally analyzed on the HALO™ image analysis platform. (3) Results: Eleven cases were EBV+, 49 cases MMRd, and 349 cases EBV-MMRpGCs. The highest rate of PD-L1 positivity was seen in EBV+GCs, followed by MMRdGCs and EBV-MMRpGCs (81.8%, 73.5%, and 27.8%, respectively). EBV+ and MMRdGCs also demonstrated increased numbers and proximity of CD8+ TILs to tumor cells compared to EBV-MMRpGCs (<i<p</i< < 0.001 each). PD-L1 status positively correlated with the total numbers of CD8+ TILs and their proximity to tumor cells in all subtypes, including EBV-MMRpGCs (<i<p</i< < 0.001 each). A total of 28.4% of EBV-MMRpGCs showed high CD8+ TILs independent of PD-L1. (4) Conclusions: PD-L1 and CD8 immunohistochemistry, supplemented by digital image analysis, may identify EBV-MMRpGCs with high immunoreactivity indices, indicating susceptibility to immunotherapy.
abstractGer	(1) Background: EBV-positive and mismatch repair-deficient (MMRd) gastric cancers (GCs) show higher levels of tumor-infiltrating lymphocytes (TILs) and PD-L1 expression and thus a more profound response to immunotherapy. However, the majority of GCs are EBV-negative (EBV−) and MMR proficient (MMRp). We analyzed PD-L1 expression and TILs in EBV-MMRpGCs in comparison to EBV-positive (EBV+) and MMRdGCs to identify an immunogenic phenotype susceptible to immunotherapy. (2) Methods: A next-generation tissue microarray of 409 primary resected GCs was analyzed by Epstein-Barr encoding region (EBER) in situ hybridization for MSH1, PMS2, MSH2, MSH6, PD-L1, and CD8 immunohistochemistry. PD-L1 positivity was defined as a combined positive score (CPS) of ≥1. CD8+ TILs and their proximity to cancer cells were digitally analyzed on the HALO™ image analysis platform. (3) Results: Eleven cases were EBV+, 49 cases MMRd, and 349 cases EBV-MMRpGCs. The highest rate of PD-L1 positivity was seen in EBV+GCs, followed by MMRdGCs and EBV-MMRpGCs (81.8%, 73.5%, and 27.8%, respectively). EBV+ and MMRdGCs also demonstrated increased numbers and proximity of CD8+ TILs to tumor cells compared to EBV-MMRpGCs (<i<p</i< < 0.001 each). PD-L1 status positively correlated with the total numbers of CD8+ TILs and their proximity to tumor cells in all subtypes, including EBV-MMRpGCs (<i<p</i< < 0.001 each). A total of 28.4% of EBV-MMRpGCs showed high CD8+ TILs independent of PD-L1. (4) Conclusions: PD-L1 and CD8 immunohistochemistry, supplemented by digital image analysis, may identify EBV-MMRpGCs with high immunoreactivity indices, indicating susceptibility to immunotherapy.
abstract_unstemmed	(1) Background: EBV-positive and mismatch repair-deficient (MMRd) gastric cancers (GCs) show higher levels of tumor-infiltrating lymphocytes (TILs) and PD-L1 expression and thus a more profound response to immunotherapy. However, the majority of GCs are EBV-negative (EBV−) and MMR proficient (MMRp). We analyzed PD-L1 expression and TILs in EBV-MMRpGCs in comparison to EBV-positive (EBV+) and MMRdGCs to identify an immunogenic phenotype susceptible to immunotherapy. (2) Methods: A next-generation tissue microarray of 409 primary resected GCs was analyzed by Epstein-Barr encoding region (EBER) in situ hybridization for MSH1, PMS2, MSH2, MSH6, PD-L1, and CD8 immunohistochemistry. PD-L1 positivity was defined as a combined positive score (CPS) of ≥1. CD8+ TILs and their proximity to cancer cells were digitally analyzed on the HALO™ image analysis platform. (3) Results: Eleven cases were EBV+, 49 cases MMRd, and 349 cases EBV-MMRpGCs. The highest rate of PD-L1 positivity was seen in EBV+GCs, followed by MMRdGCs and EBV-MMRpGCs (81.8%, 73.5%, and 27.8%, respectively). EBV+ and MMRdGCs also demonstrated increased numbers and proximity of CD8+ TILs to tumor cells compared to EBV-MMRpGCs (<i<p</i< < 0.001 each). PD-L1 status positively correlated with the total numbers of CD8+ TILs and their proximity to tumor cells in all subtypes, including EBV-MMRpGCs (<i<p</i< < 0.001 each). A total of 28.4% of EBV-MMRpGCs showed high CD8+ TILs independent of PD-L1. (4) Conclusions: PD-L1 and CD8 immunohistochemistry, supplemented by digital image analysis, may identify EBV-MMRpGCs with high immunoreactivity indices, indicating susceptibility to immunotherapy.
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_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 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	7, p 1736
title_short	Interspatial Distribution of Tumor and Immune Cells in Correlation with PD-L1 in Molecular Subtypes of Gastric Cancers
url	https://doi.org/10.3390/cancers14071736 https://doaj.org/article/106228609a3a4cb4900e33f8fcde2980 https://www.mdpi.com/2072-6694/14/7/1736 https://doaj.org/toc/2072-6694
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author2	Kirsten D. Mertz Beat Gloor Rupert Langer
author2Str	Kirsten D. Mertz Beat Gloor Rupert Langer
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up_date	2024-07-03T22:32:25.647Z
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