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

被引：9

作者：

Sato, Kei ^{[1
,2
]}

Mimaki, Sachiyo ^{[3
]}

Yamashita, Riu ^{[3
]}

Togashi, Yosuke ^{[4
]}

Naito, Tomoyuki ^{[5
]}

Udagawa, Hibiki ^{[5
]}

Katsumata, Shinya ^{[2
]}

Nakasone, Shoko ^{[2
]}

Miyoshi, Tomohiro ^{[2
]}

Tane, Kenta ^{[2
]}

Aokage, Keiju ^{[2
]}

Sugano, Masato ^{[6
,7
]}

Kojima, Motohiro ^{[1
]}

Fujii, Satoshi ^{[1
]}

Kuwata, Takeshi ^{[6
,7
]}

Ochiai, Atsushi ^{[8
]}

Goto, Koichi ^{[5
]}

Tsuboi, Masahiro ^{[2
]}

Tsuchihara, Katsuya ^{[3
]}

Ishii, Genichiro ^{[1
]}

机构：

[1] Natl Canc Ctr, Exploratory Oncol Res & Clin Trial Ctr, Div Pathol, 6-5-1 Kashiwanoha, Kashiwa, Chiba 2778577, Japan

[2] Natl Canc Ctr Hosp East, Dept Thorac Surg, Kashiwa, Chiba, Japan

[3] Exploratory Oncol Res & Clin Trial Ctr, Natl Canc Ctr, Div Translat Informat, Kashiwa, Chiba, Japan

[4] Natl Canc Ctr, Exploratory Oncol Res & Clin Trial Ctr, Res Inst, Div Canc Immunol, Kashiwa, Chiba, Japan

[5] Natl Canc Ctr Hosp East, Dept Thorac Oncol, Kashiwa, Chiba, Japan

[6] Natl Canc Ctr Hosp East, Dept Pathol, Kashiwa, Chiba, Japan

[7] Natl Canc Ctr Hosp East, Clin Labs, Kashiwa, Chiba, Japan

[8] Natl Canc Ctr, Exploratory Oncol Res & Clin Trial Ctr, Kashiwa, Chiba, Japan

来源：

LUNG CANCER | 2020年 / 147卷

关键词：

Cigarette smoking; Whole exome sequencing; Smoking signature; Immune microenvironment; Lung adenocarcinoma; REGULATORY T-CELLS; CANCER; ENTEROPATHY; INDUCTION;

D O I：

10.1016/j.lungcan.2020.06.029

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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 SSadenocarcinomas (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 SStumors, 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 SSadenocarcinomas (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.

引用

页码：12 / 20

页数：9

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