Reprogramming Immunosuppressive Myeloid Cells Facilitates Immunotherapy for Colorectal Cancer

ABSTRACT: Immune checkpoint blockade (ICB) has a limited effect on colorectal cancer, underlining the requirement of co-targeting the complementary mechanisms. Here, we identified prostaglandin E2 (PGE2) receptor 4 (EP4) as the master regulator of immunosuppressive myeloid cells (IMCs), which are the major driver of resistance to ICB therapy. PGE2-bound EP4 promotes the differentiation of immunosuppressive M2 macrophages and myeloid-derived suppressor cells (MDSCs) and reduces the expansion of immunostimulated M1 macrophages. To explore the immunotherapeutic role of EP4 signaling, we developed a novel and selective EP4 antagonist TP-16. TP-16 effectively blocked the function of IMCs and enhanced cytotoxic T cell-mediated tumor elimination in vivo. Cell co-culture experiments revealed that TP-16 prom

SUBMITTER: Dr. Weiqiang Lu 

PROVIDER: S-SCDT-EMM-2020-12798 | biostudies-other |

REPOSITORIES: biostudies-other