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 (T_IM cells). T_IM 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 T_IM 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.

免疫疗法在外周循环 T 细胞中引发全身抗肿瘤免疫反应。然而，器官之间的 T 细胞运输回路及其对抗肿瘤免疫的贡献仍然很大程度上未知。在这里，我们在多个小鼠白血病模型中显示，骨髓（BM）中白血病细胞的高度浸润刺激CD8 ⁺ CD44 ⁺ CD62L ⁺中央记忆T细胞转变为CD8 ⁺ CD44 ^– CD62L ^– T细胞，称为器官间迁移T 细胞（T _IM细胞）。 T _IM细胞在白血病发生过程中通过上调整合素 β ₇和下调 CXC 基序趋化因子受体 3 从 BM 移动到肠道。在免疫原性化疗后，这些骨髓来源的 T _IM细胞通过整合素 α ₄ -血管细胞粘附分子 1 相互作用从肠道返回骨髓。阻断 CXC 基序趋化因子受体 3 功能可通过增强 T 细胞运输来增强针对白血病的免疫反应。这种现象也可以在白血病患者中观察到。总之，我们发现了一个未被识别的 T 细胞肠-BM 运输回路，该回路有助于免疫原性化疗的抗肿瘤作用。