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

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...

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Autores principales: Hiltbrunner, Stefanie, Cords, Lena, Kasser, Sabrina, Freiberger, Sandra N., Kreutzer, Susanne, Toussaint, Nora C., Grob, Linda, Opitz, Isabelle, Messerli, Michael, Zoche, Martin, Soltermann, Alex, Rechsteiner, Markus, van den Broek, Maries, Bodenmiller, Bernd, Curioni-Fontecedro, Alessandra
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10449840/
https://www.ncbi.nlm.nih.gov/pubmed/37620318
http://dx.doi.org/10.1038/s41467-023-40745-5
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author Hiltbrunner, Stefanie
Cords, Lena
Kasser, Sabrina
Freiberger, Sandra N.
Kreutzer, Susanne
Toussaint, Nora C.
Grob, Linda
Opitz, Isabelle
Messerli, Michael
Zoche, Martin
Soltermann, Alex
Rechsteiner, Markus
van den Broek, Maries
Bodenmiller, Bernd
Curioni-Fontecedro, Alessandra
author_facet Hiltbrunner, Stefanie
Cords, Lena
Kasser, Sabrina
Freiberger, Sandra N.
Kreutzer, Susanne
Toussaint, Nora C.
Grob, Linda
Opitz, Isabelle
Messerli, Michael
Zoche, Martin
Soltermann, Alex
Rechsteiner, Markus
van den Broek, Maries
Bodenmiller, Bernd
Curioni-Fontecedro, Alessandra
author_sort Hiltbrunner, Stefanie
collection PubMed
description 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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spelling pubmed-104498402023-08-26 Acquired resistance to anti-PD1 therapy in patients with NSCLC associates with immunosuppressive T cell phenotype Hiltbrunner, Stefanie Cords, Lena Kasser, Sabrina Freiberger, Sandra N. Kreutzer, Susanne Toussaint, Nora C. Grob, Linda Opitz, Isabelle Messerli, Michael Zoche, Martin Soltermann, Alex Rechsteiner, Markus van den Broek, Maries Bodenmiller, Bernd Curioni-Fontecedro, Alessandra Nat Commun Article 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. Nature Publishing Group UK 2023-08-24 /pmc/articles/PMC10449840/ /pubmed/37620318 http://dx.doi.org/10.1038/s41467-023-40745-5 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Hiltbrunner, Stefanie
Cords, Lena
Kasser, Sabrina
Freiberger, Sandra N.
Kreutzer, Susanne
Toussaint, Nora C.
Grob, Linda
Opitz, Isabelle
Messerli, Michael
Zoche, Martin
Soltermann, Alex
Rechsteiner, Markus
van den Broek, Maries
Bodenmiller, Bernd
Curioni-Fontecedro, Alessandra
Acquired resistance to anti-PD1 therapy in patients with NSCLC associates with immunosuppressive T cell phenotype
title Acquired resistance to anti-PD1 therapy in patients with NSCLC associates with immunosuppressive T cell phenotype
title_full Acquired resistance to anti-PD1 therapy in patients with NSCLC associates with immunosuppressive T cell phenotype
title_fullStr Acquired resistance to anti-PD1 therapy in patients with NSCLC associates with immunosuppressive T cell phenotype
title_full_unstemmed Acquired resistance to anti-PD1 therapy in patients with NSCLC associates with immunosuppressive T cell phenotype
title_short Acquired resistance to anti-PD1 therapy in patients with NSCLC associates with immunosuppressive T cell phenotype
title_sort acquired resistance to anti-pd1 therapy in patients with nsclc associates with immunosuppressive t cell phenotype
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10449840/
https://www.ncbi.nlm.nih.gov/pubmed/37620318
http://dx.doi.org/10.1038/s41467-023-40745-5
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