Acquired resistance to anti-PD1 therapy in patients with NSCLC associates with immunosuppressive T cell phenotype

Abstract Immune checkpoint inhibitor treatment has the potential to prolong survival in non-small cell lung cancer (NSCLC), however, some of the patients develop resistance following initial response. Here, we analyze the immune phenotype of matching tumor samples from a cohort of NSCLC patients sho...
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Autor*in:	Stefanie Hiltbrunner [verfasserIn] Lena Cords [verfasserIn] Sabrina Kasser [verfasserIn] Sandra N. Freiberger [verfasserIn] Susanne Kreutzer [verfasserIn] Nora C. Toussaint [verfasserIn] Linda Grob [verfasserIn] Isabelle Opitz [verfasserIn] Michael Messerli [verfasserIn] Martin Zoche [verfasserIn] Alex Soltermann [verfasserIn] Markus Rechsteiner [verfasserIn] Maries van den Broek [verfasserIn] Bernd Bodenmiller [verfasserIn] Alessandra Curioni-Fontecedro [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2023

Übergeordnetes Werk:	In: Nature Communications - Nature Portfolio, 2016, 14(2023), 1, Seite 14
Übergeordnetes Werk:	volume:14 ; year:2023 ; number:1 ; pages:14

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.1038/s41467-023-40745-5

Katalog-ID:	DOAJ092891454

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allfields	10.1038/s41467-023-40745-5 doi (DE-627)DOAJ092891454 (DE-599)DOAJc99e4e76f6b544649dae1c58e4b5b5c4 DE-627 ger DE-627 rakwb eng Stefanie Hiltbrunner verfasserin aut Acquired resistance to anti-PD1 therapy in patients with NSCLC associates with immunosuppressive T cell phenotype 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Immune checkpoint inhibitor treatment has the potential to prolong survival in non-small cell lung cancer (NSCLC), however, some of the patients develop resistance following initial response. Here, we analyze the immune phenotype of matching tumor samples from a cohort of NSCLC patients showing good initial response to immune checkpoint inhibitors, followed by acquired resistance at later time points. By using imaging mass cytometry and whole exome and RNA sequencing, we detect two patterns of resistance¨: One group of patients is characterized by reduced numbers of tumor-infiltrating CD8+ T cells and reduced expression of PD-L1 after development of resistance, whereas the other group shows high CD8+ T cell infiltration and high expression of PD-L1 in addition to markedly elevated expression of other immune-inhibitory molecules. In two cases, we detect downregulation of type I and II IFN pathways following progression to resistance, which could lead to an impaired anti-tumor immune response. This study thus captures the development of immune checkpoint inhibitor resistance as it progresses and deepens our mechanistic understanding of immunotherapy response in NSCLC. Science Q Lena Cords verfasserin aut Sabrina Kasser verfasserin aut Sandra N. Freiberger verfasserin aut Susanne Kreutzer verfasserin aut Nora C. Toussaint verfasserin aut Linda Grob verfasserin aut Isabelle Opitz verfasserin aut Michael Messerli verfasserin aut Martin Zoche verfasserin aut Alex Soltermann verfasserin aut Markus Rechsteiner verfasserin aut Maries van den Broek verfasserin aut Bernd Bodenmiller verfasserin aut Alessandra Curioni-Fontecedro verfasserin aut In Nature Communications Nature Portfolio, 2016 14(2023), 1, Seite 14 (DE-627)626457688 (DE-600)2553671-0 20411723 nnns volume:14 year:2023 number:1 pages:14 https://doi.org/10.1038/s41467-023-40745-5 kostenfrei https://doaj.org/article/c99e4e76f6b544649dae1c58e4b5b5c4 kostenfrei https://doi.org/10.1038/s41467-023-40745-5 kostenfrei https://doaj.org/toc/2041-1723 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_211 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_2110 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_4335 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 14 2023 1 14
spelling	10.1038/s41467-023-40745-5 doi (DE-627)DOAJ092891454 (DE-599)DOAJc99e4e76f6b544649dae1c58e4b5b5c4 DE-627 ger DE-627 rakwb eng Stefanie Hiltbrunner verfasserin aut Acquired resistance to anti-PD1 therapy in patients with NSCLC associates with immunosuppressive T cell phenotype 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Immune checkpoint inhibitor treatment has the potential to prolong survival in non-small cell lung cancer (NSCLC), however, some of the patients develop resistance following initial response. Here, we analyze the immune phenotype of matching tumor samples from a cohort of NSCLC patients showing good initial response to immune checkpoint inhibitors, followed by acquired resistance at later time points. By using imaging mass cytometry and whole exome and RNA sequencing, we detect two patterns of resistance¨: One group of patients is characterized by reduced numbers of tumor-infiltrating CD8+ T cells and reduced expression of PD-L1 after development of resistance, whereas the other group shows high CD8+ T cell infiltration and high expression of PD-L1 in addition to markedly elevated expression of other immune-inhibitory molecules. In two cases, we detect downregulation of type I and II IFN pathways following progression to resistance, which could lead to an impaired anti-tumor immune response. This study thus captures the development of immune checkpoint inhibitor resistance as it progresses and deepens our mechanistic understanding of immunotherapy response in NSCLC. Science Q Lena Cords verfasserin aut Sabrina Kasser verfasserin aut Sandra N. Freiberger verfasserin aut Susanne Kreutzer verfasserin aut Nora C. Toussaint verfasserin aut Linda Grob verfasserin aut Isabelle Opitz verfasserin aut Michael Messerli verfasserin aut Martin Zoche verfasserin aut Alex Soltermann verfasserin aut Markus Rechsteiner verfasserin aut Maries van den Broek verfasserin aut Bernd Bodenmiller verfasserin aut Alessandra Curioni-Fontecedro verfasserin aut In Nature Communications Nature Portfolio, 2016 14(2023), 1, Seite 14 (DE-627)626457688 (DE-600)2553671-0 20411723 nnns volume:14 year:2023 number:1 pages:14 https://doi.org/10.1038/s41467-023-40745-5 kostenfrei https://doaj.org/article/c99e4e76f6b544649dae1c58e4b5b5c4 kostenfrei https://doi.org/10.1038/s41467-023-40745-5 kostenfrei https://doaj.org/toc/2041-1723 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_211 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_2110 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_4335 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 14 2023 1 14
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allfieldsGer	10.1038/s41467-023-40745-5 doi (DE-627)DOAJ092891454 (DE-599)DOAJc99e4e76f6b544649dae1c58e4b5b5c4 DE-627 ger DE-627 rakwb eng Stefanie Hiltbrunner verfasserin aut Acquired resistance to anti-PD1 therapy in patients with NSCLC associates with immunosuppressive T cell phenotype 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Immune checkpoint inhibitor treatment has the potential to prolong survival in non-small cell lung cancer (NSCLC), however, some of the patients develop resistance following initial response. Here, we analyze the immune phenotype of matching tumor samples from a cohort of NSCLC patients showing good initial response to immune checkpoint inhibitors, followed by acquired resistance at later time points. By using imaging mass cytometry and whole exome and RNA sequencing, we detect two patterns of resistance¨: One group of patients is characterized by reduced numbers of tumor-infiltrating CD8+ T cells and reduced expression of PD-L1 after development of resistance, whereas the other group shows high CD8+ T cell infiltration and high expression of PD-L1 in addition to markedly elevated expression of other immune-inhibitory molecules. In two cases, we detect downregulation of type I and II IFN pathways following progression to resistance, which could lead to an impaired anti-tumor immune response. This study thus captures the development of immune checkpoint inhibitor resistance as it progresses and deepens our mechanistic understanding of immunotherapy response in NSCLC. Science Q Lena Cords verfasserin aut Sabrina Kasser verfasserin aut Sandra N. Freiberger verfasserin aut Susanne Kreutzer verfasserin aut Nora C. Toussaint verfasserin aut Linda Grob verfasserin aut Isabelle Opitz verfasserin aut Michael Messerli verfasserin aut Martin Zoche verfasserin aut Alex Soltermann verfasserin aut Markus Rechsteiner verfasserin aut Maries van den Broek verfasserin aut Bernd Bodenmiller verfasserin aut Alessandra Curioni-Fontecedro verfasserin aut In Nature Communications Nature Portfolio, 2016 14(2023), 1, Seite 14 (DE-627)626457688 (DE-600)2553671-0 20411723 nnns volume:14 year:2023 number:1 pages:14 https://doi.org/10.1038/s41467-023-40745-5 kostenfrei https://doaj.org/article/c99e4e76f6b544649dae1c58e4b5b5c4 kostenfrei https://doi.org/10.1038/s41467-023-40745-5 kostenfrei https://doaj.org/toc/2041-1723 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_211 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_2110 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_4335 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 14 2023 1 14
allfieldsSound	10.1038/s41467-023-40745-5 doi (DE-627)DOAJ092891454 (DE-599)DOAJc99e4e76f6b544649dae1c58e4b5b5c4 DE-627 ger DE-627 rakwb eng Stefanie Hiltbrunner verfasserin aut Acquired resistance to anti-PD1 therapy in patients with NSCLC associates with immunosuppressive T cell phenotype 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Immune checkpoint inhibitor treatment has the potential to prolong survival in non-small cell lung cancer (NSCLC), however, some of the patients develop resistance following initial response. Here, we analyze the immune phenotype of matching tumor samples from a cohort of NSCLC patients showing good initial response to immune checkpoint inhibitors, followed by acquired resistance at later time points. By using imaging mass cytometry and whole exome and RNA sequencing, we detect two patterns of resistance¨: One group of patients is characterized by reduced numbers of tumor-infiltrating CD8+ T cells and reduced expression of PD-L1 after development of resistance, whereas the other group shows high CD8+ T cell infiltration and high expression of PD-L1 in addition to markedly elevated expression of other immune-inhibitory molecules. In two cases, we detect downregulation of type I and II IFN pathways following progression to resistance, which could lead to an impaired anti-tumor immune response. This study thus captures the development of immune checkpoint inhibitor resistance as it progresses and deepens our mechanistic understanding of immunotherapy response in NSCLC. Science Q Lena Cords verfasserin aut Sabrina Kasser verfasserin aut Sandra N. Freiberger verfasserin aut Susanne Kreutzer verfasserin aut Nora C. Toussaint verfasserin aut Linda Grob verfasserin aut Isabelle Opitz verfasserin aut Michael Messerli verfasserin aut Martin Zoche verfasserin aut Alex Soltermann verfasserin aut Markus Rechsteiner verfasserin aut Maries van den Broek verfasserin aut Bernd Bodenmiller verfasserin aut Alessandra Curioni-Fontecedro verfasserin aut In Nature Communications Nature Portfolio, 2016 14(2023), 1, Seite 14 (DE-627)626457688 (DE-600)2553671-0 20411723 nnns volume:14 year:2023 number:1 pages:14 https://doi.org/10.1038/s41467-023-40745-5 kostenfrei https://doaj.org/article/c99e4e76f6b544649dae1c58e4b5b5c4 kostenfrei https://doi.org/10.1038/s41467-023-40745-5 kostenfrei https://doaj.org/toc/2041-1723 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_211 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_2110 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_4335 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 14 2023 1 14
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authorswithroles_txt_mv	Stefanie Hiltbrunner @@aut@@ Lena Cords @@aut@@ Sabrina Kasser @@aut@@ Sandra N. Freiberger @@aut@@ Susanne Kreutzer @@aut@@ Nora C. Toussaint @@aut@@ Linda Grob @@aut@@ Isabelle Opitz @@aut@@ Michael Messerli @@aut@@ Martin Zoche @@aut@@ Alex Soltermann @@aut@@ Markus Rechsteiner @@aut@@ Maries van den Broek @@aut@@ Bernd Bodenmiller @@aut@@ Alessandra Curioni-Fontecedro @@aut@@
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author	Stefanie Hiltbrunner
spellingShingle	Stefanie Hiltbrunner misc Science misc Q Acquired resistance to anti-PD1 therapy in patients with NSCLC associates with immunosuppressive T cell phenotype
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topic_title	Acquired resistance to anti-PD1 therapy in patients with NSCLC associates with immunosuppressive T cell phenotype
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title	Acquired resistance to anti-PD1 therapy in patients with NSCLC associates with immunosuppressive T cell phenotype
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author_browse	Stefanie Hiltbrunner Lena Cords Sabrina Kasser Sandra N. Freiberger Susanne Kreutzer Nora C. Toussaint Linda Grob Isabelle Opitz Michael Messerli Martin Zoche Alex Soltermann Markus Rechsteiner Maries van den Broek Bernd Bodenmiller Alessandra Curioni-Fontecedro
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title_sort	acquired resistance to anti-pd1 therapy in patients with nsclc associates with immunosuppressive t cell phenotype
title_auth	Acquired resistance to anti-PD1 therapy in patients with NSCLC associates with immunosuppressive T cell phenotype
abstract	Abstract Immune checkpoint inhibitor treatment has the potential to prolong survival in non-small cell lung cancer (NSCLC), however, some of the patients develop resistance following initial response. Here, we analyze the immune phenotype of matching tumor samples from a cohort of NSCLC patients showing good initial response to immune checkpoint inhibitors, followed by acquired resistance at later time points. By using imaging mass cytometry and whole exome and RNA sequencing, we detect two patterns of resistance¨: One group of patients is characterized by reduced numbers of tumor-infiltrating CD8+ T cells and reduced expression of PD-L1 after development of resistance, whereas the other group shows high CD8+ T cell infiltration and high expression of PD-L1 in addition to markedly elevated expression of other immune-inhibitory molecules. In two cases, we detect downregulation of type I and II IFN pathways following progression to resistance, which could lead to an impaired anti-tumor immune response. This study thus captures the development of immune checkpoint inhibitor resistance as it progresses and deepens our mechanistic understanding of immunotherapy response in NSCLC.
abstractGer	Abstract Immune checkpoint inhibitor treatment has the potential to prolong survival in non-small cell lung cancer (NSCLC), however, some of the patients develop resistance following initial response. Here, we analyze the immune phenotype of matching tumor samples from a cohort of NSCLC patients showing good initial response to immune checkpoint inhibitors, followed by acquired resistance at later time points. By using imaging mass cytometry and whole exome and RNA sequencing, we detect two patterns of resistance¨: One group of patients is characterized by reduced numbers of tumor-infiltrating CD8+ T cells and reduced expression of PD-L1 after development of resistance, whereas the other group shows high CD8+ T cell infiltration and high expression of PD-L1 in addition to markedly elevated expression of other immune-inhibitory molecules. In two cases, we detect downregulation of type I and II IFN pathways following progression to resistance, which could lead to an impaired anti-tumor immune response. This study thus captures the development of immune checkpoint inhibitor resistance as it progresses and deepens our mechanistic understanding of immunotherapy response in NSCLC.
abstract_unstemmed	Abstract Immune checkpoint inhibitor treatment has the potential to prolong survival in non-small cell lung cancer (NSCLC), however, some of the patients develop resistance following initial response. Here, we analyze the immune phenotype of matching tumor samples from a cohort of NSCLC patients showing good initial response to immune checkpoint inhibitors, followed by acquired resistance at later time points. By using imaging mass cytometry and whole exome and RNA sequencing, we detect two patterns of resistance¨: One group of patients is characterized by reduced numbers of tumor-infiltrating CD8+ T cells and reduced expression of PD-L1 after development of resistance, whereas the other group shows high CD8+ T cell infiltration and high expression of PD-L1 in addition to markedly elevated expression of other immune-inhibitory molecules. In two cases, we detect downregulation of type I and II IFN pathways following progression to resistance, which could lead to an impaired anti-tumor immune response. This study thus captures the development of immune checkpoint inhibitor resistance as it progresses and deepens our mechanistic understanding of immunotherapy response in NSCLC.
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title_short	Acquired resistance to anti-PD1 therapy in patients with NSCLC associates with immunosuppressive T cell phenotype
url	https://doi.org/10.1038/s41467-023-40745-5 https://doaj.org/article/c99e4e76f6b544649dae1c58e4b5b5c4 https://doaj.org/toc/2041-1723
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author2Str	Lena Cords Sabrina Kasser Sandra N. Freiberger Susanne Kreutzer Nora C. Toussaint Linda Grob Isabelle Opitz Michael Messerli Martin Zoche Alex Soltermann Markus Rechsteiner Maries van den Broek Bernd Bodenmiller Alessandra Curioni-Fontecedro
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