Comprehensive Analysis of the Immune Microenvironment in Checkpoint Inhibitor Pneumonitis

• Published in: Frontiers in immunology 2022-01, Vol.12, p.818492-818492
• Main Authors: Lin, Xinqing, Deng, Jiaxi, Deng, Haiyi, Yang, Yilin, Sun, Ni, Zhou, Maolin, Qin, Yinyin, Xie, Xiaohong, Li, Shiyue, Zhong, Nanshan, Song, Yong, Zhou, Chengzhi
• Format: Article
• Language: English
• Subjects: aberrant pathway activation; Biomarkers; Carcinoma, Non-Small-Cell Lung - complications; Carcinoma, Non-Small-Cell Lung - diagnosis; Carcinoma, Non-Small-Cell Lung - drug therapy; Cellular Microenvironment - genetics; Cellular Microenvironment - immunology; checkpoint inhibitor pneumonitis; Disease Susceptibility; Drug Resistance, Neoplasm - drug effects; Gene Expression Profiling; Gene Expression Regulation - drug effects; Humans; immune check inhibitor (ICI); Immune Checkpoint Inhibitors - adverse effects; Immune Checkpoint Inhibitors - therapeutic use; immune infiltration; immune microenvironment; Immunology; Immunophenotyping; Inflammation Mediators - metabolism; Lung Neoplasms - complications; Lung Neoplasms - diagnosis; Lung Neoplasms - drug therapy; Lymphocytes, Tumor-Infiltrating - immunology; Lymphocytes, Tumor-Infiltrating - metabolism; Pneumonia - diagnosis; Pneumonia - etiology; Tumor Microenvironment - immunology
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2021.818492

While immune checkpoint inhibitors (ICIs) are a beacon of hope for non-small cell lung cancer (NSCLC) patients, they can also cause adverse events, including checkpoint inhibitor pneumonitis (CIP). Research shows that the inflammatory immune microenvironment plays a vital role in the development of CIP. However, the role of the immune microenvironment (IME) in CIP is still unclear. We collected a cohort of NSCLC patients treated with ICIs that included eight individuals with CIP (CIP group) and 29 individuals without CIP (Control group). CIBERSORT and the xCell algorithm were used to evaluate the proportion of immune cells. Gene set enrichment analysis (GSEA) and single-sample GSEA (ssGSEA) were used to evaluate pathway activity. The ridge regression algorithm was used to analyze drug sensitivity. CIBERSORT showed significantly upregulated memory B cells, CD8+ T cells, and M1 Macrophages in the CIP group. The number of memory resting CD4+ T cells and resting NK cells in the CIP group was also significantly lower than in the Control group. The XCell analysis showed a higher proportion of Class-switched memory B-cells and M1 Macrophages in the CIP group. Pathway analysis showed that the CIP group had high activity in their immune and inflammatory response pathways and low activity in their immune exhaustion related pathway. In this study, we researched CIP patients who after ICIs treatment developed an inflammatory IME, which is characterized by significantly increased activated immune cells and expression of inflammatory molecules, as well as downregulated immunosuppressive lymphocytes and signaling pathways. The goal was to develop theoretical guidance for clinical guidelines for the treatment of CIP in the future.