Association between the mutational smoking signature and the immune microenvironment in lung adenocarcinoma

Kei Sato, Sachiyo Mimaki, Riu Yamashita, Yosuke Togashi, Tomoyuki Naito, Hibiki Udagawa, Shinya Katsumata, Shoko Nakasone, Tomohiro Miyoshi, Kenta Tane, Keiju Aokage, Masato Sugano, Motohiro Kojima, Satoshi Fujii, Takeshi Kuwata, Atsushi Ochiai, Koichi Goto, Masahiro Tsuboi, Katsuya Tsuchihara, Genichiro Ishii

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

Objectives: Mutational signatures associated with tobacco smoking (mutational smoking signatures: SS) are characterized mainly by C > A mutations. The aim of this study was to characterize the association between the tumor immune microenvironment and the SS in lung adenocarcinoma. Methods: Lung adenocarcinomas surgically resected from 96 patients, for which whole exome sequencing data was available, were included in the study. We extracted the SS from whole exome sequencing data, calculated the weights of SS using deconstructSigs, and compared the clinicopathological features of SS positive (SS+) and negative (SS-) adenocarcinomas. We selected 18 tumor pairs from SS + and SS- adenocarcinomas (sex, EGFR mutation, and tumor size-matched) and examined the expression of five immune markers (CD20, CD8, FOXP3, CD204, and PD-L1) by immunohistochemistry. Results: Of 96 specimens, there were 33 (34 %) SS + adenocarcinoma tumors. The smoking index significantly correlated with the weight of the SS (R = 0.43). Between SS + and SS- tumors, there was no significant difference in clinicopathological factors excluding smoking history. Immunohistochemistry revealed that the number of FOXP3 + T cells in SS + adenocarcinomas was significantly higher than that in the SS- adenocarcinomas (median number 58 vs. 36, p < 0.01). Also, the number of CD20 + B cells in SS + adenocarcinomas was significantly higher than that in the SS- adenocarcinomas (median number 77 vs. 29, p < 0.01); however; these phenomena could not be confirmed when stratified by smoking history. Conclusion: In lung adenocarcinoma, SS is associated with an immunosuppressive tumor microenvironment.

Original languageEnglish
Pages (from-to)12-20
Number of pages9
JournalLung Cancer
Volume147
DOIs
Publication statusPublished - Sep 2020
Externally publishedYes

Keywords

  • Cigarette smoking
  • Immune microenvironment
  • Lung adenocarcinoma
  • Smoking signature
  • Whole exome sequencing

ASJC Scopus subject areas

  • Oncology
  • Pulmonary and Respiratory Medicine
  • Cancer Research

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