Abstract 5585: Inhibition of CSF1R enhances the antitumor efficacy of DC derived exosomes by modulating immunosuppressive tumor microenvironment

Abstract

Abstract Dendritic cell (DC) derived exosomes (Dex) provide many advantages over DC vaccines such as cost effectiveness, stability, sensitivity to the systemic microenvironment. Though, Dex showed better therapeutic outcome in murine models, however, desired outcome was not achieved in clinical trials as it failed to induce robust immunity to modulate the immunosuppressive tumor microenvironment (TME). Colony stimulating factor-1 (CSF-1) binds to its receptor (CSF-1R) and recruits tumor associated macrophages (TAMs) and myeloid derived suppressor cells (MDSCs) in the TME which eventually creates the tumor immunosuppressive. Hence, in this study we used PLX-3397, a small molecule inhibitor of CSF-1R to enhance the antitumor efficacy of Dex. In a syngenic B16-F10murine melanoma model, we found that the combination treatment delayed the tumor growth and improved the survival compare to the mono therapy. In TME, the combination treatment significantly depleted the TAMs and MDSCs and increased the infiltration of lymphocytes (TILs). Additionally, Th1 population were found significantly higher in tumor as well as in spleen with mice received both Dex and PLX3397. In conclusion, PLX-3397 enhanced the in vivo antitumor efficacy of Dex by modulating the immunosuppressive microenvironment in tumor. Citation Format: Anjali Barnwal, Jayanta Bhattacharyya, Bushra Ateeq. Inhibition of CSF1R enhances the antitumor efficacy of DC derived exosomes by modulating immunosuppressive tumor microenvironment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5585.