Combining radiation and the ATR inhibitor berzosertib activates STING signaling and enhances immunotherapy via inhibiting SHP1 function in colorectal cancer.

ABSTRACT:

Background

Immune checkpoint inhibitors (ICIs) targeting programmed cell death protein 1 (PD-1) and programmed death-ligand 1 (PD-L1) have shown a moderate response in colorectal cancer (CRC) with deficient mismatch repair (dMMR) functions and poor response in patients with proficient MMR (pMMR). pMMR tumors are generally immunogenically "cold", emphasizing combination strategies to turn the "cold" tumor "hot" to enhance the efficacy of ICIs. ATR inhibitors (ATRi) have been proven to cooperate with radiation to promote antitumor immunity, but it is unclear whether ATRi could facilitate the efficacy of IR and ICI combinations in CRCs. This study aimed to investigate the efficacy of combining ATRi, irradiation (IR), and anti-PD-L1 antibodies in CRC mouse models with different microsa

SUBMITTER: Liu C 

PROVIDER: S-EPMC10091106 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature