Chromosome Missegregation Triggers Tumor Cell Pyroptosis and Enhances Anti-Tumor Immunotherapy in Colorectal Cancer.

ABSTRACT: Immune checkpoint inhibitor (ICI) therapy is a promising anti-tumor therapeutic strategy; however, its efficacy in solid tumors is limited. Chromosome missegregation is common in various solid tumors; however, its role in tumor progression remains poorly understood, and its correlation with ICI is yet to be explored. Here, it is found that increased chromosome missegregation promotes tumor immune microenvironment, and eventually immunotherapeutic efficacy, by triggering pyroptosis. yin yang 2 (YY2) is identified as a mitotic checkpoint regulator, which promotes chromosome missegregation by upregulating BUB1B transcription. Increased chromosome missegregation promoted the formation of micronuclei and release of double-stranded DNA (dsDNA) into the cytosol, triggering an AIM2-mediated cytoso

SUBMITTER: Duan W 

PROVIDER: S-EPMC11948012 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature