Dynamic evolution and antitumor mechanisms of CXCR6+CD8+ T cells in small cell lung cancer treated with low-dose radiotherapy and immunotherapy

被引：0
作者：
Guo Lin [1 ]
Zhuoran Yao [2 ]
Kai Kang [1 ]
Ren Luo [2 ]
Linglu Yi [1 ]
You Lu [2 ]
机构：
[1] Division of Thoracic Tumor Multimodality Treatment and Department of Radiation Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu
[2] Laboratory of Clinical Cell Therapy, West China Hospital, Sichuan University, Chengdu
[3] Frontiers Medical Center, Tianfu Jincheng Laboratory, Chengdu
来源：
Journal of Translational Medicine | / 23卷 / 1期
基金：
中国博士后科学基金;
关键词：
CD8-positive T-lymphocytes; Immunotherapy; Radiotherapy; Small-cell lung cancer; Tumor-infiltrating;
D O I：
10.1186/s12967-025-06450-1
中图分类号：
学科分类号：
摘要：
Background: Patients with small-cell lung cancer (SCLC) have the poor prognosis. Current research suggested that low-dose radiotherapy (LDRT) combined with immunotherapy can enhance the immunogenicity of tumor cells, thereby improving antigen presentation and promoting the intratumoral infiltration of CD8+ T cells, which significantly extends the survival of patients. However, the change trajectory of T cells, and the mechanisms underlying the promotion of intratumoral infiltration of CD8+ T cells, and the enhancement of their cytotoxic functions remain to be elucidated. Methods: To delineate the dynamic changes of T cells, we collected tumors from Kaede tumor-bearing mice that had undergone radioimmunotherapy. Using flow cytometry, we sorted intratumoral-infiltrating immune cells, which were required for single-cell RNA sequencing, at various time points (Kaede Red: derived from tumor-draining lymph node [TDLN]). The results obtained from the sequencing analysis were further validated through experiments, such as flow cytometry, immunofluorescence, and analysis of clinical cohort data. Results: Here, we observed stem-like T cells migrating from the TDLN to the tumor site and differentiating into effector phenotypes within the tumor. Dendritic cells (DCs) are the key cluster that induces the differentiation of stem-like T cell into effector phenotypes. Moreover, SCLC patients with a high infiltration of tumor-specific CXCR6+CD8+ T cells exhibited a supportive TME and longer survival time (P < 0.001). Conclusions: This study delineates the change trajectory of CD8+ T cells, identifies the crucial role of DCs in T cell differentiation, and highlights the significance of tumor-specific CXCR6+CD8+ T cells in anti-tumor immunity. Future therapeutic strategies for SCLC could focus on enhancing the infiltration of activated DCs and CXCR6+CD8+ T cells within the tumor microenvironment to improve treatment efficacy. © The Author(s) 2025.
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