Single-cell transcriptome analysis deciphers the CD74-mediated immune evasion and tumour growth in lung squamous cell carcinoma with chronic obstructive pulmonary disease.

Autor: Wang D; Precision Medicine Research Center, Precision Medicine Key Laboratory of Sichuan Province, State Key Laboratory of Respiratory Health and Multimorbidity, West China Hospital, Sichuan University, Chengdu, Sichuan, China.; Department of Respiratory and Critical Care Medicine, Precision Medicine Center, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, Sichuan, China.; Research Units of West China, Chinese Academy of Medical Sciences, West China Hospital, Chengdu, Sichuan, China., Li S; Department of Respiratory and Critical Care Medicine, Precision Medicine Center, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, Sichuan, China.; Department of Respiratory and Critical Care Medicine, National Clinical Research Center for Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China., Yang Z; Department of Nephrology, West China Hospital, Sichuan University, Chengdu, Sichuan, China., Yu C; Frontiers Science Center for Disease-Related Molecular Network, Laboratory of Omics Technology and Bioinformatics, West China Hospital, Sichuan University, Chengdu, Sichuan, China., Wu P; Department of Respiratory Health, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, Sichuan, China., Yang Y; Department of Respiratory Health, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, Sichuan, China., Zhang R; Department of Respiratory and Critical Care Medicine, Precision Medicine Center, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, Sichuan, China., Li Q; Department of Respiratory Health, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, Sichuan, China., Yang J; Center of Growth, Metabolism, and Aging, Key Laboratory of Bio-Resources and Eco-Environment, College of Life Sciences, Sichuan University, Chengdu, Sichuan, China., Li H; National Chengdu Center for Safety Evaluation of Drugs, State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, China., Ji G; Health Management Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China., Wang Y; Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, China., Xie K; Precision Medicine Research Center, Precision Medicine Key Laboratory of Sichuan Province, State Key Laboratory of Respiratory Health and Multimorbidity, West China Hospital, Sichuan University, Chengdu, Sichuan, China., Liu Y; Lung Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China., Wang K; Department of Respiratory and Critical Care Medicine, Precision Medicine Center, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, Sichuan, China., Zhu D; Lung Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China., Zhang W; Precision Medicine Research Center, Precision Medicine Key Laboratory of Sichuan Province, State Key Laboratory of Respiratory Health and Multimorbidity, West China Hospital, Sichuan University, Chengdu, Sichuan, China., Liu D; Department of Respiratory and Critical Care Medicine, Precision Medicine Center, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, Sichuan, China., Chen B; Precision Medicine Research Center, Precision Medicine Key Laboratory of Sichuan Province, State Key Laboratory of Respiratory Health and Multimorbidity, West China Hospital, Sichuan University, Chengdu, Sichuan, China., Li W; Precision Medicine Research Center, Precision Medicine Key Laboratory of Sichuan Province, State Key Laboratory of Respiratory Health and Multimorbidity, West China Hospital, Sichuan University, Chengdu, Sichuan, China.; Department of Respiratory and Critical Care Medicine, Precision Medicine Center, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, Sichuan, China.; Research Units of West China, Chinese Academy of Medical Sciences, West China Hospital, Chengdu, Sichuan, China.
Jazyk: angličtina
Zdroj: Clinical and translational medicine [Clin Transl Med] 2024 Aug; Vol. 14 (8), pp. e1786.
DOI: 10.1002/ctm2.1786
Abstrakt: Background: Chronic obstructive pulmonary disease (COPD) contributes to the incidence and prognosis of lung cancer. The presence of COPD significantly increases the risk of lung squamous cell carcinoma (LSCC). COPD may promote an immunosuppressive microenvironment in LSCC by regulating the expression of immune-inhibitory factors in T cells, although the mechanisms remain unclear. In this study, we aimed to decipher the tumour microenvironment signature for LSCC with COPD at a single-cell level.
Methods: We performed single-cell RNA sequencing on tumour tissues from LSCC with or without COPD, then investigated the features of the immune and tumour cells. We employed multiple techniques, including multispectral imaging, flow cytometry, tissue microarray analysis, survival analysis, co-culture systems and in vitro and in vivo treatment experiments, to validate the findings obtained from single-cell analyses.
Results: LSCC with COPD showed increased proportions of tumour-associated macrophages (TAMs) and higher levels of CD8 + T cell exhaustion molecules, which contributed to an immunosuppressive microenvironment. Further analysis revealed a critical cluster of CD74 + tumour cells that expressed both epithelial and immune cell signatures, exhibited a stronger capacity for tumorigenesis and predicted worse overall survival. Notably, migration inhibitory factor (MIF) secreted by TAMs from LSCC with COPD may promote the activation of CD74. MIF-CD74 may interact with CD8 + T cells and impair their anti-tumour activity by regulating the PI3K-STAT3-programmed cell death-1 ligand 1 signalling pathway, facilitating tumour proliferation and immune evasion.
Conclusions: Our comprehensive picture of the tumour ecosystem in LSCC with COPD provides deeper insights into relevant immune evasion mechanisms and potential targets for immunotherapy.
Highlight: Our results demonstrated higher proportions of tumour-associated macrophages (TAMs) and higher levels of exhaustion molecules in CD8 + T cells in the microenvironment of LSCC with COPD. CD74 + tumour cells were associated with poor disease prognosis. Migration inhibitory factor (MIF)-CD74 may interact with CD8 + T cells and impair their anti-tumour activity by regulating the PI3K-STAT3-PD-L1 signalling pathway, facilitating immune evasion.
(© 2024 The Author(s). Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.)
Databáze: MEDLINE
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