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.
引用
收藏
相关论文
共 70 条
  • [61] Thomas S.N., Vokali E., Lund A.W., Hubbell J.A., Swartz M.A., Targeting the tumor-draining lymph node with adjuvanted nanoparticles reshapes the anti-tumor immune response, Biomaterials, 35, 2, pp. 814-824, (2014)
  • [62] Kim G.B., Sung H.D., Nam G.H., Kim W., Kim S., Kang D., Lee E.J., Kim I.S., Design of PD-1-decorated nanocages targeting tumor-draining lymph node for promoting T cell activation, J Controll Releas Off J Controll Releas Soc, 333, pp. 328-338, (2021)
  • [63] Watany M., Badawi R., Elkhalawany W., Abd-Elsalam S., Study of dickkopf-1 (DKK-1) gene expression in hepatocellular carcinoma patients, J Clin Diagn Res JCDR, (2017)
  • [64] Li T., Pan J., Chen H., Fang Y., Sun Y., CXCR6-based immunotherapy in autoimmune, cancer and inflammatory infliction, Acta Pharm Sinica B, 12, 8, pp. 3255-3262, (2022)
  • [65] Mabrouk N., Tran T., Sam I., Pourmir I., Gruel N., Granier C., Pineau J., Gey A., Kobold S., Fabre E., Et al., CXCR6 expressing T cells: functions and role in the control of tumors, Front Immunol, 13, (2022)
  • [66] Korbecki J., Kojder K., Kapczuk P., Kupnicka P., Gawronska-Szklarz B., Gutowska I., Chlubek D., Baranowska-Bosiacka I., The effect of hypoxia on the expression of CXC chemokines and CXC chemokine receptors-a review of literature, Int J Mol Sci, 22, (2021)
  • [67] Akkaya B., Kamenyeva O., Kabat J., Kissinger R., Visualizing the dynamics of T cell-dendritic cell interactions in intact lymph nodes by multiphoton confocal microscopy, Method Mol Biol (Clifton NJ), 2304, pp. 243-263, (2021)
  • [68] Aghaei M., Khademi R., Bahreiny S.S., Saki N., The need to establish and recognize the field of clinical laboratory science (CLS) as an essential field in advancing clinical goals, Health Sci Report, 7, 8, (2024)
  • [69] Rajabi L., Ebrahimdoost M., Mohammadi S.A., Soleimani Samarkhazan H., Khamisipour G., Aghaei M., Aqueous and ethanolic extracts of Moringa oleifera leaves induce selective cytotoxicity in Raji and Jurkat cell lines by activating the P21 pathway independent of P53, Mol Biol Rep, 52, 1, (2025)
  • [70] Saki N., Haybar H., Aghaei M., Subject: motivation can be suppressed, but scientific ability cannot and should not be ignored, J Transl Med, 21, 1, (2023)
1234567