Microenvironment and Immunology CCL2/CCR2-Dependent Recruitment of Functional Antigen- Presenting Cells into Tumors upon Chemotherapy

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 CD11bþCD11cþLy6ChighLy6G MHCIIþ 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 inmice 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. Cancer Res; 74(2); 1–10. 2013 AACR.