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Systemic activation and tissue infiltration of CD8 + CX3CR1 + T cells in non-small cell lung cancer treated with neoadjuvant immune checkpoint blockade

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机构： [1]Institute of Respiratory Health, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, Sichuan, China. [2]Center of Gerontology and Geriatrics, West China Hospital, Sichuan University, Chengdu, Sichuan, China [3]Institute of Thoracic Oncology, Frontiers Science Center for Disease-related Molecular Networks, West China Hospital, Sichuan University, Chengdu, Sichuan, China. [4]Departments of Obstetrics and Gynecology and Pediatrics, West China Second University Hospital, Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, Development and Related Diseases of Women and Children Key Laboratory of Sichuan Province, Sichuan University, Chengdu, Sichuan, China. [5]Department of Pulmonary and Critical Care Medicine, West China Hospital, State Key Laboratory of Respiratory Health and Multimorbidity, Sichuan University, Chengdu, Sichuan, China. [6]Department of Pathology, West China Hospital, Sichuan University, Chengdu, Sichuan, China [7]Center for Infectious Disease and Vaccine Research, West China Hospital, Sichuan University, Chengdu, Sichuan, China [8]Lung Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China. [9]Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, China [10]Cicada Bio., Shanghai, China,Dolphin Biosciences Co. Ltd, Hangzhou, Zhejiang, China

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Neoadjuvant immune checkpoint blockade (NA-ICB) shows promise in treating resectable and locally advanced non-small cell lung cancer (NSCLC), yet the specific T cell subtypes that expand and become functionally reactivated remain incompletely characterised.We applied single-cell RNA sequencing, TCR repertoire analysis, and flow cytometry to tumour, paired normal lung tissue, and peripheral blood samples from 26 NA-ICB-treated and 14 treatment-naïve NSCLC patients to investigate responsive T cell subtypes, their tissue origins, migration patterns, and phenotype transitions.CD8 + CX3CR1 + T cells were significantly enriched in responsive tumours, as evidenced by increased proportions (p = 0.0027) and clonal expansion in scRNA-seq, and elevated protein-level frequencies detected by flow cytometry (p = 0.021). Longitudinal analysis revealed proliferation of these cells in peripheral blood post-treatment. Shared TCR clonotypes were identified across blood and tumour samples. Pseudotime analysis indicated differentiation of these cells into exhausted and cytotoxic NK-like CD8 + T cells upon tumour infiltration.These findings suggest that CD8 + CX3CR1 + T cells may represent circulating cytotoxic precursors associated with effective NA-ICB responses, suggesting their potential as predictive biomarkers and therapeutic targets for adoptive cell therapy.© 2025. The Author(s), under exclusive licence to Springer Nature Limited.

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出版当年[2025]版：

大类 | 2 区

医学

小类 | 2 区肿瘤学

最新[2025]版：

大类 | 2 区

医学

小类 | 2 区肿瘤学

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第一作者机构： [1]Institute of Respiratory Health, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, Sichuan, China. [2]Center of Gerontology and Geriatrics, West China Hospital, Sichuan University, Chengdu, Sichuan, China

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通讯作者：

通讯机构： [1]Institute of Respiratory Health, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, Sichuan, China. [8]Lung Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China. [9]Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, China [10]Cicada Bio., Shanghai, China,Dolphin Biosciences Co. Ltd, Hangzhou, Zhejiang, China

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