PBRM1 deficiency enhances PD1 immunotherapeutic sensitivity via chromosomal accessibility in colorectal cancer.

ABSTRACT: Rationale: Tumor cell epigenetics, especially chromosome accessibility, has been reported to be closely related to the tumor immune landscape and immunotherapy. However, the exact mechanism remains unknown. Methods: Whole-exome sequencing was used to analyze 13 colorectal tumor samples treated with PD1 immunotherapy. The assays for transposase-accessible chromatin using sequencing (ATAC-seq) and RNA sequencing were used to detect tumor cells' chromosome accessibility status and screen regulatory pathways. Results: Polybromo-1 (PBRM1) was one of the 12 genes with the highest frequency of somatic mutations associated with immunotherapy sensitivity. PBRM1/Pbrm1 deficiency in colorectal cancer promoted PD-1 immunotherapy sensitivity and chemotaxis of CD8⁺ T and

SUBMITTER: Li R 

PROVIDER: S-EPMC11905143 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature