Super-enhancer receives signals from the extracellular matrix to induce PD-L1-mediated immune evasion via integrin/BRAF/TAK1/ERK/ETV4 signaling.

ABSTRACT:

Objective

PD-L1 and PD-L2 expression levels determine immune evasion and the therapeutic efficacy of immune checkpoint blockade. The factors that drive inducible PD-L1 expression have been extensively studied, but mechanisms that result in constitutive PD-L1 expression in cancer cells are largely unknown.

Methods

DNA elements were deleted in cells by CRISPR/Cas9-mediated knockout. Protein function was inhibited by chemical inhibitors. Protein levels were examined by Western blot, mRNA levels were examined by real-time RT-PCR, and surface protein expression was determined by cellular immunofluorescence and flow cytometry. Immune evasion was examined by in vitro T cell-mediated killing.

Results

We determined the core regions (chr9: 5, 496, 378-5, 499, 663) of a p

SUBMITTER: Ma P 

PROVIDER: S-EPMC9196059 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature