Vaccine-induced tumor regression requires a dynamic cooperation between T cells and myeloid cells at the tumor site.
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.
Inserm, U1016, Institut Cochin, Paris, France.|Cnrs, UMR8104, Paris, France.|Université Paris Descartes, Sorbonne Paris Cité, Paris, France.|Equipe Labellisée "Ligue contre le Cancer", Paris, France.
Maxime
M
Thoreau
Singapore Immunology Network, BMSI, A-STAR, Singapore.
HweiXian Leong
HL
Penny
Singapore Immunology Network, BMSI, A-STAR, Singapore.
KarWai
K
Tan
Inserm, U1016, Institut Cochin, Paris, France.|Cnrs, UMR8104, Paris, France.|Université Paris Descartes, Sorbonne Paris Cité, Paris, France.|Equipe Labellisée "Ligue contre le Cancer", Paris, France.
Fabienne
F
Regnier
Inserm, U1016, Institut Cochin, Paris, France.|Cnrs, UMR8104, Paris, France.|Université Paris Descartes, Sorbonne Paris Cité, Paris, France.|Equipe Labellisée "Ligue contre le Cancer", Paris, France.
Julia Miriam
JM
Weiss
Singapore Immunology Network, BMSI, A-STAR, Singapore.
Bernett
B
Lee
Institut Curie, Paris, France.|INSERM U1143, Paris, France.|CNRS UMR3666, Paris, France.
Ludger
L
Johannes
Institut Curie, Paris, France.|INSERM U1143, Paris, France.|CNRS UMR3666, Paris, France.
Estelle
E
Dransart
Inserm, U1016, Institut Cochin, Paris, France.|Cnrs, UMR8104, Paris, France.|Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
Agnès
A
Le Bon
Singapore Immunology Network, BMSI, A-STAR, Singapore.
Jean-Pierre
JP
Abastado
Inserm U970, PARCC, Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
Eric
E
Tartour
Inserm, U1016, Institut Cochin, Paris, France.|Cnrs, UMR8104, Paris, France.|Université Paris Descartes, Sorbonne Paris Cité, Paris, France.|Equipe Labellisée "Ligue contre le Cancer", Paris, France.
Alain
A
Trautmann
Inserm, U1016, Institut Cochin, Paris, France.|Cnrs, UMR8104, Paris, France.|Université Paris Descartes, Sorbonne Paris Cité, Paris, France.|Equipe Labellisée "Ligue contre le Cancer", Paris, France.
Nadège
N
Bercovici
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D019496:Cancer Vaccines / Q000276:immunology*; D002450:Cell Communication / Q000276:immunology; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D022423:Myeloid Cells / Q000276:immunology*; D009374:Neoplasms, Experimental / Q000276:immunology*; D059467:Transcriptome
D019496:Cancer Vaccines
T lymphocytes; imaging; myeloid cells; tumor regression; vaccine