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Sci Rep. 2018 Oct 1;8(1):14576. doi: 10.1038/s41598-018-32855-8.

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

Seo JS1,2,3,4, Kim A5,6,7, Shin JY6,8, Kim YT9,10,11.

Author information

1
Precision Medicine Center, Seoul National University Bundang Hospital, Seongnamsi, 13605, Korea. jeongsun@snu.ac.kr.
2
Genomic Medicine Institute, Medical Research Center, Seoul National University, Seoul, 03080, Republic of Korea. jeongsun@snu.ac.kr.
3
Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, 03080, Republic of Korea. jeongsun@snu.ac.kr.
4
Macrogen Inc., Seoul, 08511, Korea. jeongsun@snu.ac.kr.
5
Precision Medicine Center, Seoul National University Bundang Hospital, Seongnamsi, 13605, Korea.
6
Genomic Medicine Institute, Medical Research Center, Seoul National University, Seoul, 03080, Republic of Korea.
7
Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, 03080, Republic of Korea.
8
Macrogen Inc., Seoul, 08511, Korea.
9
Genomic Medicine Institute, Medical Research Center, Seoul National University, Seoul, 03080, Republic of Korea. ytkim@snu.ac.kr.
10
Seoul National University Cancer Research Institute, Seoul, Republic of Korea. ytkim@snu.ac.kr.
11
Department of Thoracic and Cardiovascular Surgery, Seoul National University Hospital, Seoul, 03080, Korea. ytkim@snu.ac.kr.

Abstract

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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