CCL2/CCR2-dependent recruitment of functional antigen-presenting cells into tumors upon chemotherapy

Yuting Ma, Stephen R. Mattarollo, Sandy Adjemian, Heng Yang, Laetitia Aymeric, Dalil Hannani, João Paulo Portela Catani, Helene Duret, Michele W L Teng, Oliver Kepp, Yidan Wang, Antonella Sistigu, Joachim L. Schultze, Gautier Stoll, Lorenzo Galluzzi, Laurence Zitvogel, Mark J. Smyth, Guido Kroemer

Research output: Contribution to journalArticle

Abstract

The therapeutic efficacy of anthracyclines relies, at least partially, on the induction of a dendritic cell- and T-lymphocyte-dependent anticancer immune response. Here, we show that anthracycline-based chemotherapy promotes the recruitment of functional CD11b CD11c+ Ly6Chigh Ly6G - MHCII+ dendritic cell-like antigenpresenting cells (APC) into the tumor bed, but not into lymphoid organs. Accordingly, draining lymph nodes turned out to be dispensable for the proliferation of tumor antigen-specific T cells within neoplastic lesions as induced by anthracyclines. In addition, we found that tumors treated with anthracyclines manifest increased expression levels of the chemokine Ccl2. Such a response is important as neoplasms growing in Ccl2-/- mice failed to accumulate dendritic cell-like APCs in response to chemotherapy. Moreover, cancers developing in mice lacking Ccl2 or its receptor (Ccr2) exhibited suboptimal therapeutic responses to anthracycline-based chemotherapy. Altogether, our results underscore the importance of the CCL2/CCR2 signaling axis for therapeutic anticancer immune responses as elicited by immunogenic chemotherapy.

Original languageEnglish
Pages (from-to)436-445
Number of pages10
JournalCancer Research
Volume74
Issue number2
DOIs
Publication statusPublished - Jan 15 2014

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ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Ma, Y., Mattarollo, S. R., Adjemian, S., Yang, H., Aymeric, L., Hannani, D., Catani, J. P. P., Duret, H., Teng, M. W. L., Kepp, O., Wang, Y., Sistigu, A., Schultze, J. L., Stoll, G., Galluzzi, L., Zitvogel, L., Smyth, M. J., & Kroemer, G. (2014). CCL2/CCR2-dependent recruitment of functional antigen-presenting cells into tumors upon chemotherapy. Cancer Research, 74(2), 436-445. https://doi.org/10.1158/0008-5472.CAN-13-1265