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

Oncotarget. 2015 Sep 29;6(29):27832-46. doi: 10.18632/oncotarget.4940.


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.

Keywords: T lymphocytes; imaging; myeloid cells; tumor regression; vaccine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD8-Positive T-Lymphocytes / immunology*
  • Cancer Vaccines / immunology*
  • Cell Communication / immunology
  • Flow Cytometry
  • Fluorescent Antibody Technique
  • Lymphocytes, Tumor-Infiltrating / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Myeloid Cells / immunology*
  • Neoplasms, Experimental / immunology*
  • Transcriptome


  • Cancer Vaccines