Data from CCL2/CCR2-Dependent Recruitment of Functional Antigen-Presenting Cells into Tumors upon Chemotherapy

<div>Abstract<p>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<sup>+</sup>CD11c<sup>+</sup>Ly6C<sup>high</sup>Ly6G<sup>−</sup>MHCII<sup>+</sup> dendritic cell–like antigen-presenting 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 <i>Ccl2<sup>−/−</sup></i> 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. <i>Cancer Res; 74(2); 436–45. ©2013 AACR</i>.</p></div>