Carfilzomib modulates tumor microenvironment to potentiate immune checkpoint therapy for cancer

ABSTRACT: Impressive clinical benefit is seen in clinic with PD-1 inhibitors on portion of cancer patients. Yet, there remains an urgent need to develop effective synergizers to expand their clinical application. Tumor associated macrophage (TAM), a type of M2-polarized macrophage, eliminates or suppresses T cell mediated anti-tumor responses. Transforming TAMs into M1 macrophages is an attractive strategy of anti-tumor therapy. Here we conducted a high-throughput screening and found that Carfilzomib potently drove M2 macrophages to express M1 cytokines, phagocytose tumor cells and present antigens to T cells. Mechanistically, Carfilzomib elicited unfolded protein response (UPR), activated IRE1α to recruit TRAF2, and activated NF-κB to transcribe genes encoding M1 markers in M2 macrophages. In vivo,

SUBMITTER: Dr. Qian Zhou 

PROVIDER: S-SCDT-EMM-2021-14502 | biostudies-other |

REPOSITORIES: biostudies-other