Xiaoxiang Zhou, Ziming Jiang, Yanhong Ren, Yunzhi Zhou, Lei Deng, Zhenting Liu, Sijin Sun, Jieli Zhang, Wenyang Liu, Yin Yang, Wenting Ren, Yanfeng Wang, Hongxia Li, Yiqun Li, Fei Ma, Nan Bi, Luhua Wang, Yibo Gao, Jie He
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引用次数: 0
Abstract
Background: Checkpoint inhibitor pneumonitis (CIP) is the leading cause of treatment-related deaths for immune checkpoint inhibitor (ICI) combination therapies. CIP is problematic to diagnose and differentiate, particularly from radiation pneumonitis (RP), due to the lack of mechanistic distinctions between them.
Methods: Using single-cell RNA sequencing (scRNA-seq) and single-cell T cell receptor sequencing (scTCR-seq), we characterize the cellular landscape of bronchoalveolar lavage fluid (BALF) and peripheral blood from a discovery cohort (seven CIP, six RP, and six treatment-naive controls) and a validation cohort (five patients receiving combined ICI and radiotherapy who were diagnosed with RP).
Findings: We report a striking accumulation of alveolar CD8+ exhausted T cells (Texs) in CIP. The alveolar CD8+ Texs of CIP primarily differentiate from tissue-resident ZNF683hi CD8+ T cells, whereas those of RP predominantly originate from peripherally related GZMKhi CD8+ T cells. These findings were further validated in a prospectively enrolled validation cohort and ultimately guided successful clinical decisions regarding ICI rechallenge.
Conclusions: These results highlight distinct cellular and molecular features in CIP and RP, thereby providing insights into clinical decision-making regarding ICI rechallenge in lung cancer patients.
Funding: This study was supported by the National Natural Science Foundation of China.
期刊介绍：
Med is a flagship medical journal published monthly by Cell Press, the global publisher of trusted and authoritative science journals including Cell, Cancer Cell, and Cell Reports Medicine. Our mission is to advance clinical research and practice by providing a communication forum for the publication of clinical trial results, innovative observations from longitudinal cohorts, and pioneering discoveries about disease mechanisms. The journal also encourages thought-leadership discussions among biomedical researchers, physicians, and other health scientists and stakeholders. Our goal is to improve health worldwide sustainably and ethically.
Med publishes rigorously vetted original research and cutting-edge review and perspective articles on critical health issues globally and regionally. Our research section covers clinical case reports, first-in-human studies, large-scale clinical trials, population-based studies, as well as translational research work with the potential to change the course of medical research and improve clinical practice.
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