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  • Open Access

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

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Journal for ImmunoTherapy of Cancer20153 (Suppl 2) :P293

https://doi.org/10.1186/2051-1426-3-S2-P293

  • Published:

Keywords

  • Tumor Site
  • Myeloid Cell
  • Tumor Regression
  • Cell Infiltrate
  • Cancer Immunotherapy

Most cancer immunotherapies under present investigation are based on the belief that cytotoxic T cells are the most important anti-tumoral immune cells, whereas intratumoral macrophages would rather play a protumoral role. We have challenged this antagonistic point of view and searched on the contrary for complementary contributions provided 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 intratumoral accumulation of CD8+ T cells. Conversely, CD8+ T cells and IFNg production activate myeloid cells and 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 eliminate tumor cells by TNFα release and phagocytosis. Altogether, our data suggest new strategies to improve the efficiency of cancer immunotherapies, by promoting intratumoral cooperation between macrophages and T cells.

Authors’ Affiliations

(1)
Institut Cochin, Inserm U1016, CNRS UMR8104, Univ. Paris Descartes, Sorbonne Paris Cité, Equipe labellisée “Ligue contre le Cancer”, Paris, France
(2)
Singapore Immunology Network, BMSI, A-STAR, Singapore, Singapore
(3)
Institut Curie, INSERM U1143, CNRS UMR3666, Paris, France
(4)
Inserm U970, PARCC, Université Paris Descartes, Sorbonne Paris Cité, Paris, France

Copyright

© Thoreau et al. 2015

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

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