The next-generation BET inhibitor, PLX51107, delays melanoma growth in a CD8-mediated manner.

ABSTRACT: Epigenetic agents such as bromodomain and extra-terminal region inhibitors (BETi) slow tumor growth via tumor intrinsic alterations; however, their effects on antitumor immunity remain unclear. A recent advance is the development of next-generation BETi that are potent and display a favorable half-life. Here, we tested the BETi, PLX51107, for immune-based effects on tumor growth in BRAF V600E melanoma syngeneic models. PLX51107 delayed melanoma tumor growth and increased activated, proliferating, and functional CD8+ T cells in tumors leading to CD8+ T-cell-mediated tumor growth delay. PLX51107 decreased Cox2 expression, increased dendritic cells, and lowered PD-L1, FasL, and IDO-1 expression in the tumor microenvironment. Importantly, PLX51107 delayed the growth of tumors that progressed o

SUBMITTER: Erkes DA 

PROVIDER: S-EPMC6697571 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature