近日，上海交通大学段才闻等研究人员合作发现，CD8⁺T细胞在肠道和骨髓间的迁移回路影响抗肿瘤免疫。2024年7月22日，《自然—细胞生物学》杂志在线发表了这项成果。

研究人员在多个小鼠白血病模型中发现，高度浸润骨髓（BM）的白血病细胞刺激CD8⁺CD44⁺CD62L⁺中心记忆T细胞转变为CD8⁺CD44^–CD62L^–T细胞，称为器官间迁移性T细胞（T_IM细胞）。在白血病发生过程中，T_IM细胞通过上调整合素β₇和下调C-X-C基序趋化因子受体3，从BM迁移到肠道。在免疫原性化疗期间，这些来自BM的T_IM细胞通过整合素α₄–血管细胞黏附分子1相互作用从肠道返回BM。

阻断C-X-C基序趋化因子受体3功能可以通过增强T细胞迁移来提升对白血病的免疫反应。这种现象也在白血病患者中观察到。总之，研究人员发现了一条未被识别的肠道–BM T细胞迁移回路，这一回路对免疫原性化疗的抗肿瘤效果做出了贡献。

据悉，免疫疗法在外周循环的T细胞中引发系统性抗肿瘤免疫反应。然而，器官之间T细胞迁移回路及其对抗肿瘤免疫的贡献仍然在很大程度上未知。

附：英文原文

Title: Trafficking circuit of CD8+ T cells between the intestine and bone marrow governs antitumour immunity

Author: Shi, Rong-Yi, Zhou, Neng, Xuan, Li, Jiang, Zhong-Hui, Xia, Jing, Zhu, Jian-Min, Chen, Kai-Ming, Zhou, Guo-Li, Yu, Guo-Pan, Zhang, Jun, Huang, Chuanxin, Liang, Ai-Bin, Liang, Kai-Wei, Zhang, Hao, Chen, Jian-Feng, Zhang, Dachuan, Zhong, Yi, Liu, Qi-Fa, Chen, Guo-Qiang, Duan, Cai-Wen

Issue&Volume: 2024-07-22

Abstract: Immunotherapy elicits a systemic antitumour immune response in peripheral circulating T cells. However, the T cell trafficking circuit between organs and their contributions to antitumour immunity remain largely unknown. Here we show in multiple mouse leukaemia models that high infiltration of leukaemic cells in bone marrow (BM) stimulates the transition of CD8+CD44+CD62L+ central memory T cells into CD8+CD44–CD62L– T cells, designated as inter-organ migratory T cells (TIM cells). TIM cells move from the BM to the intestine by upregulating integrin β7 and downregulating C-X-C motif chemokine receptor 3 during leukaemogenesis. Upon immunogenic chemotherapy, these BM-derived TIM cells return from the intestine to the BM through integrin α4–vascular cell adhesion molecule 1 interaction. Blocking C-X-C motif chemokine receptor 3 function boosts the immune response against leukaemia by enhancing T cell trafficking. This phenomenon can also be observed in patients with leukaemia. In summary, we identify an unrecognized intestine–BM trafficking circuit of T cells that contributes to the antitumour effects of immunogenic chemotherapy.

DOI: 10.1038/s41556-024-01462-3

Source: https://www.nature.com/articles/s41556-024-01462-3