biostudies-literatureUnknownAli H<h4>Background</h4>Glioblastoma (GBM) exhibits profound resistance to CD8⁺ T cell-mediated killing, yet the tumor-intrinsic mechanisms driving this immune evasion remain poorly defined. Our earlier study revealed Checkpoint Kinase 2 (Chek2) as the driver of CD8+ T cell resistance. This study investigates the immunomodulatory program exerted by the CHK2-YBX1&YBX3 regulatory hub.<h4>Methods</h4>Protein-protein interactions were investigated through immunoprecipitation (IP) followed by mass spectrometry (MS) and phosphoproteomics. Single gene knockout of CHEK2, Y-box-binding protein 1 (YBX1), and Y-box-binding protein 3 (YBX3) were generated in human and mouse glioma cells. Transcriptomic and epigenetic alterations were characterized by bulk RNA sequencing and chromatin immunoprecipitation seNeuro-oncologynoaf227https://www.ebi.ac.uk/biostudies/studies/S-EPMC12930254biostudies-literatureYBX1&amp;YBX3 as novel targets to potentiate immune checkpoint blockade response in gliomas.PMC12930254Ali HLee-Chang CZhou NTulaiha RDmello CYeeravalli RHenrik Heiland DChen LMishra SHabashy Kvan Hijfte LSonabend AMZhou YKim KSDuffy JWang LTiek DMHorbinski CAhmed AKarri VSong XArrieta VAfalseYBX1&amp;YBX3 as novel targets to potentiate immune checkpoint blockade response in gliomas.<h4>Background</h4>Glioblastoma (GBM) exhibits profound resistance to CD8⁺ T cell-mediated killing, yet the tumor-intrinsic mechanisms driving this immune evasion remain poorly defined. Our earlier study revealed Checkpoint Kinase 2 (Chek2) as the driver of CD8+ T cell resistance. This study investigates the immunomodulatory program exerted by the CHK2-YBX1&YBX3 regulatory hub.<h4>Methods</h4>Protein-protein interactions were investigated through immunoprecipitation (IP) followed by mass spectrometry (MS) and phosphoproteomics. Single gene knockout of CHEK2, Y-box-binding protein 1 (YBX1), and Y-box-binding protein 3 (YBX3) were generated in human and mouse glioma cells. Transcriptomic and epigenetic alterations were characterized by bulk RNA sequencing and chromatin immunoprecipitation se2025-01-01T00:00:00Z2025 Sep2026-07-09T12:23:30.552Z2026-07-09T11:17:43.335ZS-EPMC129302544102550110.1093/neuonc/noaf227