Distinct immune microenvironment of lung adenocarcinoma in never-smokers from smokers

Wenxin Luo; Zhen Zeng; Yang Jin; Lan Yang; Ting Fan; Zhoufeng Wang; Yitong Pan; Ying Yang; Menglin Yao; Yangqian Li; Xue Xiao; Gang Wang; Chengdi Wang; Shuai Chang; Guowei Che; Li Zhang; Yalun Li; Yong Peng; Weimin Li

doi:10.1016/j.xcrm.2023.101078

Distinct immune microenvironment of lung adenocarcinoma in never-smokers from smokers

Cell Rep Med. 2023 Jun 20;4(6):101078. doi: 10.1016/j.xcrm.2023.101078. Epub 2023 Jun 9.

Authors

Wenxin Luo¹, Zhen Zeng², Yang Jin², Lan Yang¹, Ting Fan², Zhoufeng Wang³, Yitong Pan², Ying Yang³, Menglin Yao³, Yangqian Li³, Xue Xiao³, Gang Wang³, Chengdi Wang¹, Shuai Chang⁴, Guowei Che⁴, Li Zhang³, Yalun Li¹, Yong Peng⁵, Weimin Li⁶

Affiliations

¹ Department of Respiratory and Critical Care Medicine, Institute of Respiratory Health, Precision Medicine Center, Precision Medicine Key Laboratory of Sichuan Province, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu 610041, China.
² Laboratory of Molecular Oncology, Frontiers Science Center for Disease-related Molecular Network, Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China.
³ Precision Medicine Center, Precision Medicine Key Laboratory of Sichuan Province, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu 610041, China.
⁴ Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu 610041, China.
⁵ Laboratory of Molecular Oncology, Frontiers Science Center for Disease-related Molecular Network, Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China. Electronic address: yongpeng@scu.edu.cn.
⁶ Department of Respiratory and Critical Care Medicine, Institute of Respiratory Health, Precision Medicine Center, Precision Medicine Key Laboratory of Sichuan Province, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu 610041, China. Electronic address: weimi003@scu.edu.cn.

Abstract

Lung cancer in never-smokers (LCINS) presents clinicopathological and molecular features distinct from that in smokers. Tumor microenvironment (TME) plays important roles in cancer progression and therapeutic response. To decipher the difference in TME between never-smoker and smoker lung cancers, we conduct single-cell RNA sequencing on 165,753 cells from 22 treatment-naive lung adenocarcinoma (LUAD) patients. We find that the dysfunction of alveolar cells induced by cigarette smoking contributes more to the aggressiveness of smoker LUADs, while the immunosuppressive microenvironment exerts more effects on never-smoker LUADs' aggressiveness. Moreover, the SPP1^hi pro macrophage is identified to be another independent source of monocyte-derived macrophage. Importantly, higher expression of immune checkpoint CD47 and lower expression of major histocompatibility complex (MHC)-I in cancer cells of never-smoker LUADs imply that CD47 may be a better immunotherapy target for LCINS. Therefore, this study reveals the difference of tumorigenesis between never-smoker and smoker LUADs and provides a potential immunotherapy strategy for LCINS.

Keywords: CD47; adenocarcinoma; lung cancer in never-smokers; single-cell RNA sequencing; tumor microenvironment.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adenocarcinoma of Lung*
CD47 Antigen
Humans
Lung Neoplasms* / genetics
Smokers
Tumor Microenvironment

Substances

CD47 Antigen