Subclonal accumulation of immune escape mechanisms in microsatellite instability-high colorectal cancers.

ABSTRACT:

Background

Intratumor heterogeneity (ITH) in microsatellite instability-high (MSI-H) colorectal cancer (CRC) has been poorly studied. We aimed to clarify how the ITH of MSI-H CRCs is generated in cancer evolution and how immune selective pressure affects ITH.

Methods

We reanalyzed public whole-exome sequencing data on 246 MSI-H CRCs. In addition, we performed a multi-region analysis from 6 MSI-H CRCs. To verify the process of subclonal immune escape accumulation, a novel computational model of cancer evolution under immune pressure was developed.

Results

Our analysis presented the enrichment of functional genomic alterations in antigen-presentation machinery (APM). Associative analysis of neoantigens indicated the generation of immune escape mechanisms via HLA alterat

SUBMITTER: Kobayashi Y 

PROVIDER: S-EPMC10539316 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature