Single-cell transcriptome sequencing reveals the immune microenvironment in bronchoalveolar lavage fluid of checkpoint inhibitor-related pneumonitis

作者：Linpeng Zheng, Feng-Lin Lin, Dingqin Cai, Longyao Zhang, Chenrui Yin, Yiying Qi, Lingyou Sun, Lingchen Li, Xiewan Chen, Jianbo Zhu, Jianguo Sun · 发表于：Cancer Immunology Immunotherapy · 年份：2025 · DOI：10.1007/s00262-025-03983-8 · 被引用次数：7 · 研究领域：Cancer Immunotherapy and Biomarkers、Lung Cancer Research Studies、Immune cells in cancer

BACKGROUND AND OBJECTIVES: Immune checkpoint inhibitors (ICIs) bring cancer patients tumor control and survival benefits, yet they also trigger immune-related adverse effects (irAEs), notably checkpoint inhibitor-related pneumonitis (CIP), affecting about 5% of patients among whom 1-2% experiencing severe grade 3 or higher pneumonitis. Current research points to potential links with T cell subset dysfunction and autoantibody increase, but the specific mechanisms underlying different grades of CIP are understudied. METHODS: Herein, we employed single-cell RNA sequencing (scRNA-seq) on bronchoalveolar lavage fluid (BALF) from CIP patients across varying severity levels, aiming to elucidate underlying immune environment and mechanisms of CIP progression at cellular and molecular levels. FINDINGS: Totally, 121,409 high qualified cells from BALF of 11 patients were annotated and categorized into five major cell types. Severe CIP (CIP-S) cases have a significant increase in the percentage of unreported epithelial cells in their bronchoalveolar lavage fluid compared with mild CIP (CIP-M) cases. These cells were defined as aberrant basaloid cells. They upregulated SOX9, increased the expression of CXCL3/5, recruited neutrophils, and activated the immune system. Additionally, macrophages in the CIP-S group had stronger antigen-presenting abilities and resulted in more CD8 + effective T cells infiltrated. CONCLUSIONS: Utilizing single-cell sequencing of BALF, we discovered an enriched ...