Mapping the genetic landscape establishing a tumor immune microenvironment favorable for anti-PD-1 response in mice and humans.

ABSTRACT: Identifying host genetic factors modulating immune checkpoint inhibitor (ICI) efficacy has been experimentally challenging because of variations in both host and tumor genomes, differences in the microbiome, and patient life exposures. Utilizing the Collaborative Cross (CC) multi-parent mouse genetic resource population, we developed an approach that fixes the tumor genomic configuration while varying host genetics. With this approach, we discovered that response to anti-PD-1 (aPD1) immunotherapy was significantly heritable in four distinct murine tumor models (H² between 0.18-0.40). For the MC38 colorectal carcinoma system (H² = 0.40), we mapped four significant ICI response quantitative trait loci (QTL) localized to mouse chromosomes (mChr) 5, 9, 15 an

SUBMITTER: Skelly DA 

PROVIDER: S-EPMC11275897 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature