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Cancer Immunol Res. 2018 Jul;6(7):848-859. doi: 10.1158/2326-6066.CIR-17-0453. Epub 2018 May 2.

Whole Exome and Transcriptome Analyses Integrated with Microenvironmental Immune Signatures of Lung Squamous Cell Carcinoma.

Seo JS#1,2,3,4, Lee JW#2,3, Kim A#2,3, Shin JY#2,4, Jung YJ5, Lee SB5, Kim YH5, Park S6, Lee HJ6, Park IK6, Kang CH6, Yun JY2,4, Kim J2,4, Kim YT7,5,6.

Author information

1
Precision Medicine Center, Seoul National University Bundang Hospital, Seongnamsi, Korea. jeongsun@snu.ac.kr ytkim@snu.ac.kr.
2
Genomic Medicine Institute (GMI), Medical Research Center, Seoul National University, Seoul, Republic of Korea.
3
Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of Korea.
4
Macrogen Inc., Seoul, Republic of Korea.
5
Seoul National University Cancer Research Institute, Seoul, Republic of Korea.
6
Department of Thoracic and Cardiovascular Surgery, Seoul National University Hospital, Seoul, Republic of Korea.
7
Genomic Medicine Institute (GMI), Medical Research Center, Seoul National University, Seoul, Republic of Korea. jeongsun@snu.ac.kr ytkim@snu.ac.kr.
#
Contributed equally

Abstract

The immune microenvironment in lung squamous cell carcinoma (LUSC) is not well understood, with interactions between the host immune system and the tumor, as well as the molecular pathogenesis of LUSC, awaiting better characterization. To date, no molecularly targeted agents have been developed for LUSC treatment. Identification of predictive and prognostic biomarkers for LUSC could help optimize therapy decisions. We sequenced whole exomes and RNA from 101 tumors and matched noncancer control Korean samples. We used the information to predict subtype-specific interactions within the LUSC microenvironment and to connect genomic alterations with immune signatures. Hierarchical clustering based on gene expression and mutational profiling revealed subtypes that were either immune defective or immune competent. We analyzed infiltrating stromal and immune cells to further characterize the tumor microenvironment. Elevated expression of macrophage 2 signature genes in the immune competent subtype confirmed that tumor-associated macrophages (TAM) linked inflammation and mutation-driven cancer. A negative correlation was evident between the immune score and the amount of somatic copy-number variation (SCNV) of immune genes (r = -0.58). The SCNVs showed a potential detrimental effect on immunity in the immune-deficient subtype. Knowledge of the genomic alterations in the tumor microenvironment could be used to guide design of immunotherapy options that are appropriate for patients with certain cancer subtypes. Cancer Immunol Res; 6(7); 848-59. ©2018 AACR.

PMID:
29720381
DOI:
10.1158/2326-6066.CIR-17-0453
[Indexed for MEDLINE]

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