{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T01:55:34Z","timestamp":1792806934615,"version":"4.5.0"},"reference-count":47,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2025,9,30]],"date-time":"2025-09-30T00:00:00Z","timestamp":1759190400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"SPORE for Translational Approaches to Brain Cancer","award":["5DP5OD021356"],"award-info":[{"award-number":["5DP5OD021356"]}]},{"name":"SPORE for Translational Approaches to Brain Cancer","award":["1R01CA245969"],"award-info":[{"award-number":["1R01CA245969"]}]},{"name":"SPORE for Translational Approaches to Brain Cancer","award":["R01NS096376-06A1"],"award-info":[{"award-number":["R01NS096376-06A1"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Glioblastoma (GBM) exhibits profound resistance to CD8\u207a 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&amp;YBX3 regulatory hub.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Protein\u2013protein 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 sequencing (ChIP-seq). Single-cell RNA sequencing and spatial transcriptomics analysis were performed to evaluate CHK2-YBX1&amp;YBX3 related phenotype in human GBM tumors. In vivo survival studies were conducted to assess the therapeutic potential of CHK2-YBX1&amp;YBX3 degradation and immune checkpoint blockade (ICB).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>CHK2, YBX1, and YBX3 exhibited reciprocal positive regulation and depletion of any of these genes resulted in derepression of pro-inflammatory gene expression. Pharmacological inhibition with the drug targeting YBX1 led to degradation of the CHK2-YBX1&amp;YBX3 hub accompanied by enhanced antigen presentation and antigen-specific CD8\u207a T cell proliferation. Combination therapy targeting CHK2-YBX1&amp;YBX3 hub and ICB significantly improved survival in preclinical glioma models.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These findings define a novel glioma-intrinsic immunosuppressive program and proposes targeting the CHK2-YBX1&amp;YBX3 hub to potentiate response to ICB in glioma.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/neuonc\/noaf227","type":"journal-article","created":{"date-parts":[[2025,9,29]],"date-time":"2025-09-29T11:33:39Z","timestamp":1759145619000},"page":"159-174","source":"Crossref","is-referenced-by-count":7,"title":["YBX1&amp;YBX3 as novel targets to potentiate immune checkpoint blockade response in gliomas"],"prefix":"10.1093","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5535-7638","authenticated-orcid":false,"given":"Heba","family":"Ali","sequence":"first","affiliation":[{"name":"Department of Neurological Surgery, Feinberg School of Medicine, Northwestern University , Chicago, IL,","place":["United States"]},{"name":"Northwestern Medicine Malnati Brain Tumor Institute of the Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University , Chicago, IL,","place":["United States"]},{"name":"Department of Zoology, Faculty of Science, Assiut University , Assiut,","place":["Egypt"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ningjia","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery, Feinberg School of Medicine, Northwestern University , Chicago, IL,","place":["United States"]},{"name":"Northwestern Medicine Malnati Brain Tumor Institute of the Lurie Comprehensive Cancer 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Querrey Institute for Epigenetics and the Department of Biochemistry and Molecular Genetics, Northwestern University Feinberg School of Medicine , Chicago, IL, (R.T., L.W.)","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vivekanudeep","family":"Karri","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery, Feinberg School of Medicine, Northwestern University , Chicago, IL,","place":["United States"]},{"name":"Northwestern Medicine Malnati Brain Tumor Institute of the Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University , Chicago, IL,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yalu","family":"Zhou","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Hypertension, Northwestern University Feinberg School of Medicine and the Feinberg Cardiovascular and Renal Research Institute , Chicago, IL,","place":["United 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