Pancancer Fine-Mapping of Mutational Intolerance Identifies CHEK1 as an Immunosuppressive Driver in Lung Adenocarcinoma - PubMed
9 hours ago
- #CHEK1
- #immunosuppression
- #lung adenocarcinoma
- Identified 1,020 mutation-intolerant genes (MIGs) across 8,096 tumors in 13 cancer types using the miDriver computational framework.
- MIGs are linked to synthetic lethality, cell-cycle progression, and clinical outcomes, with CHEK1 highlighted as a key vulnerability.
- CHEK1 suppression reduces tumor proliferation and migration, and CHEK1-high tumor cells show stem-like and immune-suppressed features.
- CHEK1 promotes MIF expression via p53 phosphorylation, driving M2-like macrophage polarization through the MIF-CD74 axis.
- Targeting the CHEK1-MIF axis reverses immunosuppression in vivo, with higher CHEK1 levels correlating with poorer response to anti-PD-1 therapy.
- MIGs, exemplified by CHEK1, are proposed as dual therapeutic targets to disrupt tumor fitness and remodel the immunosuppressive niche.