Potentiating effect of reovirus on immune checkpoint inhibition in microsatellite stable colorectal cancer.

ABSTRACT: The majority of colorectal cancers (CRCs) are microsatellite stable (MSS) and resistant to immunotherapy. The current study explores the possibility of using oncolytic reovirus to sensitize MSS CRC to immune checkpoint inhibition. While reovirus reduced metabolic activity among KRAS ^Mut cells, microarray/computational analysis revealed microsatellite status-oriented activation of immune-response pathways. Reovirus plus anti-PD-1 treatment increased cell death among MSS cells ex vivo. Reduced tumorigenicity and proliferative index, and increased apoptosis were evident among CT26 [MSS, KRAS ^Mut], but not in MC38 [microsatellite unstable/MSI, KRAS ^Wt] syngeneic mouse models under combinatorial treatment. PD-L1-PD-1 signaling axis we

SUBMITTER: Augustine T 

PROVIDER: S-EPMC9642964 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature