Splenic myeloid cells tolerize tumour-specific T cells

This study provides evidence of a central role for the spleen in the induction of T cell tolerance in tumour-bearing hosts. In several tumour models, splenectomy fully restored the activation of tumour antigen-specific T cells in tumour-draining lymph nodes. Also, the increased antitumour efficacy of adoptive T cell transfer after chemotherapy with 5-fluorouracil was shown to result from the elimination of CD11b⁺GR1^med myeloid cells in the splenic marginal zone. These immature myeloid cells — which accumulate in the spleen during tumour growth in response to CCL2 — could sample tumour-released exosomes to cross-present tumour antigens and tolerize CD8⁺ T cells. The results suggest that tumour immunotherapy could be enhanced by chemotherapeutic agents that target the highly proliferative myeloid cells in the splenic marginal zone.