Single-Cell RNA Sequencing Reveals the Tissue-Specific Immune Signatures of Lung Cancer with COPD

The carcinogenic mechanism of COPD is still unclear. We performed single-cell RNA sequencing on COPD tissues, and COPD-overlapped lung cancer tissue (LCCOPD), and enrolled the scRNA-seq data of normal lung tissues, COPD tissues, lung cancer tissues, and LCCOPD tissues from the public. Most immune cell types were significantly enriched in COPD groups. FOXP3 expression was significantly increased in LCCOPD-related T-regs and positively associated with CTLA-4 and PD-1 to form an immunosuppressive environment. Macrophages from different pathological environments show significant differences in cell composition, pseudo-time trajectories, and phenotypic dominance. COPD-related macrophages were dominated by M1-type with increased cell proliferation. LCCOPD-related macrophages, dominated by M2-type and tumor-associated macrophages, had progressively enhanced immune population chemotaxis. The overlap of COPD accelerated infiltration of T-regs and M2 macrophages, and several metabolic and cytokine pathways may be involved, such as the SREBP pathway, IFN-γ, glycolysis, and glutamine metabolism. Our study described lung cancer overlapping COPD which elucidates the role of COPD in the development of lung cancer.Funding Information: This work was supported by grants from the National Natural Science Foundation of China (No.81770095, 81700093,81800343, 8210082163), the Fundamental Research Funds for the Central Universities (No.2042021kf0081), and Science Fund for Creative Research Groups of the Natural Science Foundation of Hubei Province (No.2020CFA027).Declaration of Interests: The authors declare no conflict of interest.Ethics Approval Statement: The study was prospective clinical research, conducted by Renmin Hospital of Wuhan University and was approved by the Ethics Committee of Renmin Hospital of Wuhan University (approved number: WDRY2020-K009). All patients have fully informed the relevant research content before the experiment and the researchers guarantee that this experiment does not involve unnecessary human trauma.