Vaccine-induced tumor regression requires a dynamic cooperation between T cells and myeloid cells at the tumor site

Abstract : Most cancer immunotherapies under present investigation are based on the belief that cytotoxic T cells are the most important anti-tumoral immune cells, whereas intra-tumoral macrophages would rather play a pro-tumoral role. We have challenged this antagonistic point of view and searched for collaborative contributions by tumor-infiltrating T cells and macrophages, reminiscent of those observed in anti-infectious responses. We demonstrate that, in a model of therapeutic vaccination, cooperation between myeloid cells and T cells is indeed required for tumor rejection. Vaccination elicited an early rise of CD11b + myeloid cells that preceded and conditioned the intra-tumoral accumulation of CD8 + T cells. Conversely, CD8 + T cells and IFNγ production activated myeloid cells were required for tumor regression. A 4-fold reduction of CD8 + T cell infiltrate in CXCR3KO mice did not prevent tumor regression, whereas a reduction of tumor-infiltrating myeloid cells significantly interfered with vaccine efficiency. We show that macrophages from regressing tumors can kill tumor cells in two ways: phagocytosis and TNFα release. Altogether, our data suggest new strategies to improve the efficiency of cancer immunotherapies, by promoting intra-tumoral cooperation between macrophages and T cells.
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Oncotarget, Impact journals, 2015, 6 (29), pp.27832-46. 〈10.18632/oncotarget.4940〉
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Maxime Thoreau, Hweixian Leong Penny, Karwai Tan, Fabienne Regnier, Julia Miriam Weiss, et al.. Vaccine-induced tumor regression requires a dynamic cooperation between T cells and myeloid cells at the tumor site. Oncotarget, Impact journals, 2015, 6 (29), pp.27832-46. 〈10.18632/oncotarget.4940〉. 〈inserm-01214610〉

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