Eliciting an Immunostimulatory Tumor Microenvironment to Enhance the Antitumor Efficacy by Targeted Cancer Immunotherapy

Abstract

AbstractTumor‐associated macrophages (TAMs) in tumor microenvironment represent an ideal therapeutic target for cancer immunotherapy. A targeted cancer immunotherapy strategy through reprogramming M2 macrophages to reverse the immunosuppressive microenvironment is proposed and the antitumor effects via targeted immunostimulatory therapy are evaluated. The developed M2‐macrophage‐targeted nanoparticles (M2‐TNPs) can specially target and reprogram the M2 macrophages via polarization to the antitumor M1 phenotype. Compared with nontargeted nanoparticles, M2‐TNPs loading zoledronic acid can specifically be recognized by M2 macrophages but not other macrophages and mounted productive antitumor responses, showing enhanced antitumor efficacy by targeted immunostimulation in vitro and in vivo. Moreover, when combining the chemotherapeutic drug dacarbazine with M2‐TNPs for treatment of melanoma, a dramatic synergistic effect in cancer therapy through eliciting an immunostimulatory tumor microenvironment to restore the antitumor immunity is demonstrated. These studies provide preclinical evidence that targeted TAM‐reprogramming treatment strategies can hold tremendous promise in cancer immunotherapy.