Zhang Zhening, Zhang Lei, Wang Keqiang, Xie Tong, Zhang Xiaotian, Yu Wenyi, Li Yanyan, Shen Lin, Li Ran, Peng Zhi
Key laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Gastrointestinal Oncology, Peking University Cancer Hospital & Institute, Beijing, China.
Department of Immunobiology, Yale University School of Medicine, Yale University, New Haven, CT, USA.
NPJ Precis Oncol. 2024 Oct 5;8(1):226. doi: 10.1038/s41698-024-00715-6.
The pathophysiology of immune checkpoint inhibitor-related pneumonitis remains incompletely understood. We conducted single-cell and T-cell receptor transcriptomic sequencing on the bronchoalveolar lavage fluid from five patients with grade ≥2 immune checkpoint inhibitor-related pneumonitis. Our analyses revealed a prominent enrichment of T cells in the bronchoalveolar lavage fluid of patients with immune checkpoint inhibitor-related pneumonitis. Within the CD4 + T cell subset, Tfh-like T cells were highly enriched and exhibited signatures associated with inflammation and clonal expansion. Regulatory T cells were also enriched and displayed enhanced inhibitory functions. Within the CD8 + T-cell subset, effector memory/tissue-resident memory T cells with an elevated cytotoxic phenotype were highly infiltrated. Among myeloid cells, alveolar macrophages were depleted, while pro-inflammatory intermediate monocytes were elevated. Dendritic cells demonstrated enhanced antigen presentation capabilities. Cytokines CXCR4, CXCL13, TNF-α, IFN-α, IFN-γ, and TWEAK were elevated. Through a comprehensive single-cell analysis, we depicted the landscape of immune checkpoint inhibitor-related pneumonitis.
免疫检查点抑制剂相关肺炎的病理生理学仍未完全明确。我们对5例≥2级免疫检查点抑制剂相关肺炎患者的支气管肺泡灌洗液进行了单细胞和T细胞受体转录组测序。我们的分析显示，免疫检查点抑制剂相关肺炎患者的支气管肺泡灌洗液中T细胞显著富集。在CD4+T细胞亚群中，类滤泡辅助性T细胞高度富集，并表现出与炎症和克隆扩增相关的特征。调节性T细胞也有富集，并显示出增强的抑制功能。在CD8+T细胞亚群中，具有高细胞毒性表型的效应记忆/组织驻留记忆T细胞高度浸润。在髓样细胞中，肺泡巨噬细胞减少，而促炎中间单核细胞增加。树突状细胞表现出增强的抗原呈递能力。细胞因子CXCR4、CXCL13、TNF-α、IFN-α、IFN-γ和TWEAK升高。通过全面的单细胞分析，我们描绘了免疫检查点抑制剂相关肺炎的图景。
