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 journalArticlepeer-review

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

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Fingerprint Dive into the research topics of 'CCL2/CCR2-dependent recruitment of functional antigen-presenting cells into tumors upon chemotherapy'. Together they form a unique fingerprint.

Cite this