Chemokines as adjuvants for immunotherapy: implications for immune activation with CCL3.

INTRODUCTION: Immunotherapy embodies any approach that manipulates the immune system for therapeutic benefit. In this regard, various clinical trials have employed direct vaccination with patient-specific dendritic cells or adoptive T cell therapy to target highly aggressive tumors. Both modalities have demonstrated great specificity, an advantage that is unmatched by other treatment strategies. However, their full potential has yet to be realized. Areas covered: In this review, we provide an overview of chemokines in pathogen and anti-tumor immune responses and discuss further improving immunotherapies by arming particular chemokine axes. Expert commentary: The chemokine macrophage inflammatory protein-1 alpha (MIP-1α, CCL3) has emerged as a potent activator of both innate and adaptive responses. Specifically, CCL3 plays a critical role in recruiting distinct immune phenotypes to intratumoral sites, is a pivotal player in regulating lymph node homing of dendritic cell subsets, and induces antigen-specific T cell responses. The recent breadth of literature outlines the various interactions of CCL3 with these cellular subsets, which have now served as a basis for immunotherapeutic translation.