Table_1_Comprehensive Analysis of the Immune Microenvironment in Checkpoint Inhibitor Pneumonitis.pdf

BackgroundWhile 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.
MethodsWe 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.
ResultsCIBERSORT 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.
ConclusionsIn 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.

背景 免疫检查点抑制剂（immune checkpoint inhibitors, ICIs）是非小细胞肺癌（non-small cell lung cancer, NSCLC）患者的治疗希望之光，但该类药物亦可引发多种不良反应，其中包括免疫检查点抑制剂相关性肺炎（checkpoint inhibitor pneumonitis, CIP）。研究表明，炎症性免疫微环境在CIP的发生发展中发挥重要作用，但目前免疫微环境（immune microenvironment, IME）在CIP中的具体作用仍不明确。
方法 本研究收集了接受ICIs治疗的NSCLC患者队列，其中8例合并CIP（CIP组），29例未合并CIP（对照组）。采用CIBERSORT与xCell算法评估免疫细胞占比；通过基因集富集分析（gene set enrichment analysis, GSEA）及单样本GSEA（single-sample GSEA, ssGSEA）评估通路活性；使用岭回归（ridge regression）算法分析药物敏感性。
结果 CIBERSORT分析显示，CIP组的记忆B细胞、CD8+T细胞及M1型巨噬细胞比例显著升高；静息记忆CD4+T细胞与静息NK细胞的比例则显著低于对照组。xCell分析结果表明，CIP组的类别转换记忆B细胞及M1型巨噬细胞占比更高。通路富集分析显示，CIP组的免疫与炎症反应通路活性较高，而与免疫耗竭相关的通路活性较低。
结论 本研究针对ICIs治疗后发生CIP的NSCLC患者，揭示了其炎症性免疫微环境的特征：活化免疫细胞与炎症分子表达显著上调，免疫抑制性淋巴细胞及相关信号通路表达下调。本研究旨在为未来临床CIP治疗指南的制定提供理论依据。