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

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 (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.