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Comprehensive analysis of the tumor immune micro-environment in non-small cell lung cancer for efficacy of checkpoint inhibitor

Characterizing the molecular immune subtype and micro-environment of lung cancer is necessary to understand immunogenic interactions between infiltrating immune and stromal cells, and how tumor cells overcome immune checkpoint blockades. This study seeks to identify computational methodologies for s...

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Autores principales: Seo, Jeong-Sun, Kim, Ahreum, Shin, Jong-Yeon, Kim, Young Tae
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6167371/
https://www.ncbi.nlm.nih.gov/pubmed/30275546
http://dx.doi.org/10.1038/s41598-018-32855-8
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author Seo, Jeong-Sun
Kim, Ahreum
Shin, Jong-Yeon
Kim, Young Tae
author_facet Seo, Jeong-Sun
Kim, Ahreum
Shin, Jong-Yeon
Kim, Young Tae
author_sort Seo, Jeong-Sun
collection PubMed
description Characterizing the molecular immune subtype and micro-environment of lung cancer is necessary to understand immunogenic interactions between infiltrating immune and stromal cells, and how tumor cells overcome immune checkpoint blockades. This study seeks to identify computational methodologies for subtyping gene expression-based tumor-immune micro-environment interactions, which differentiate non-small cell lung cancer (NSCLC) into immune-defective and immune-competent subtypes. Here, 101 lung squamous cell carcinomas (LUSCs) and 87 lung adenocarcinomas (LUADs) tumor samples have been analyzed. Several micro-environmental factors differentially induce LUAD or LUSC immune subtypes, as well as immune checkpoint expression. In particular, tumor-associated macrophages (TAMs) are key immune cells play a vital role in inflammation and cancer micro-environments of LUSCs; whereas, regulatory B cells are immunosuppressive and tumorigenic in LUADs. Additionally, cytolytic activity upon CD8(+) T cell activation is decreased by the abundance of B cells and macrophages in immune-competent subtypes. Therefore, identifying immune subtypes in lung cancer and their impact on tumor micro-environment will lead to clinical tools for assessing LUADs and LUSCs in patients, as well as maximize the efficacy of immune checkpoint inhibitors.
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spelling pubmed-61673712018-10-04 Comprehensive analysis of the tumor immune micro-environment in non-small cell lung cancer for efficacy of checkpoint inhibitor Seo, Jeong-Sun Kim, Ahreum Shin, Jong-Yeon Kim, Young Tae Sci Rep Article Characterizing the molecular immune subtype and micro-environment of lung cancer is necessary to understand immunogenic interactions between infiltrating immune and stromal cells, and how tumor cells overcome immune checkpoint blockades. This study seeks to identify computational methodologies for subtyping gene expression-based tumor-immune micro-environment interactions, which differentiate non-small cell lung cancer (NSCLC) into immune-defective and immune-competent subtypes. Here, 101 lung squamous cell carcinomas (LUSCs) and 87 lung adenocarcinomas (LUADs) tumor samples have been analyzed. Several micro-environmental factors differentially induce LUAD or LUSC immune subtypes, as well as immune checkpoint expression. In particular, tumor-associated macrophages (TAMs) are key immune cells play a vital role in inflammation and cancer micro-environments of LUSCs; whereas, regulatory B cells are immunosuppressive and tumorigenic in LUADs. Additionally, cytolytic activity upon CD8(+) T cell activation is decreased by the abundance of B cells and macrophages in immune-competent subtypes. Therefore, identifying immune subtypes in lung cancer and their impact on tumor micro-environment will lead to clinical tools for assessing LUADs and LUSCs in patients, as well as maximize the efficacy of immune checkpoint inhibitors. Nature Publishing Group UK 2018-10-01 /pmc/articles/PMC6167371/ /pubmed/30275546 http://dx.doi.org/10.1038/s41598-018-32855-8 Text en © The Author(s) 2018 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/.
spellingShingle Article
Seo, Jeong-Sun
Kim, Ahreum
Shin, Jong-Yeon
Kim, Young Tae
Comprehensive analysis of the tumor immune micro-environment in non-small cell lung cancer for efficacy of checkpoint inhibitor
title Comprehensive analysis of the tumor immune micro-environment in non-small cell lung cancer for efficacy of checkpoint inhibitor
title_full Comprehensive analysis of the tumor immune micro-environment in non-small cell lung cancer for efficacy of checkpoint inhibitor
title_fullStr Comprehensive analysis of the tumor immune micro-environment in non-small cell lung cancer for efficacy of checkpoint inhibitor
title_full_unstemmed Comprehensive analysis of the tumor immune micro-environment in non-small cell lung cancer for efficacy of checkpoint inhibitor
title_short Comprehensive analysis of the tumor immune micro-environment in non-small cell lung cancer for efficacy of checkpoint inhibitor
title_sort comprehensive analysis of the tumor immune micro-environment in non-small cell lung cancer for efficacy of checkpoint inhibitor
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6167371/
https://www.ncbi.nlm.nih.gov/pubmed/30275546
http://dx.doi.org/10.1038/s41598-018-32855-8
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