{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Zhou Y"],"funding":["Parker Institute for Cancer Immunotherapy","NIAID NIH HHS","National Heart, Lung, and Blood Institute","NHLBI NIH HHS","National Cancer Institute","NCI NIH HHS","National Institutes of Health","University of Texas MD Anderson","Wilks Family Fund","Cancer Prevention and Research Institute of Texas"],"pagination":["e20221333"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9664499"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["220(2)"],"pubmed_abstract":["Immune checkpoint blockade (ICB) has revolutionized cancer treatment, yet quality of life and continuation of therapy can be constrained by immune-related adverse events (irAEs). Limited understanding of irAE mechanisms hampers development of approaches to mitigate their damage. To address this, we examined whether mice gained sensitivity to anti-CTLA-4 (αCTLA-4)-mediated toxicity upon disruption of gut homeostatic immunity. We found αCTLA-4 drove increased inflammation and colonic tissue damage in mice with genetic predisposition to intestinal inflammation, acute gastrointestinal infection, transplantation with a dysbiotic fecal microbiome, or dextran sodium sulfate administration. We identified an immune signature of αCTLA-4-mediated irAEs, including colonic neutrophil accumulation and s"],"journal":["The Journal of experimental medicine"],"pubmed_title":["Intestinal toxicity to CTLA-4 blockade driven by IL-6 and myeloid infiltration."],"pmcid":["PMC9664499"],"funding_grant_id":["R01 AI133822","P50 CA221703","P30CA016672","R01AI109294","CA016672","P30CA0166722","R01 HL158796","P30 CA008748","RP170067","T32 CA009599","RP210028","3R01CA187076-05S1","CA009599","R01AI109294-04S1","P30 CA016672","HL158796","R01AI133822","RR190017","P50CA221703","R01 AI109294","R01 CA187076"],"pubmed_authors":["Kahn LM","Wong MC","Mishra AK","Peng W","Foo WC","Peterson CB","Patel B","Whitley EM","Gubin MM","Cass SH","Wang J","Park EM","Wargo JA","Wani K","Joon AY","Arora R","Cogdill AP","Johnson SB","Ledesma DA","Diehl GE","Diab A","Zamler DB","Chen S","Pineda JE","Tang X","Wadud Khan MA","Allison JP","Watowich SS","Raso MG","Schneider S","Babcock RL","Dyevoich AM","Johnson DH","Chrisikos TT","Zhou Y","Clise-Dwyer K","Li HS","Tetzlaff MT","Medik YB","Chapman T","Zhang X","Hudgens CW","Hwu P","Ajami NJ"],"additional_accession":[]},"is_claimable":false,"name":"Intestinal toxicity to CTLA-4 blockade driven by IL-6 and myeloid infiltration.","description":"Immune checkpoint blockade (ICB) has revolutionized cancer treatment, yet quality of life and continuation of therapy can be constrained by immune-related adverse events (irAEs). Limited understanding of irAE mechanisms hampers development of approaches to mitigate their damage. To address this, we examined whether mice gained sensitivity to anti-CTLA-4 (αCTLA-4)-mediated toxicity upon disruption of gut homeostatic immunity. We found αCTLA-4 drove increased inflammation and colonic tissue damage in mice with genetic predisposition to intestinal inflammation, acute gastrointestinal infection, transplantation with a dysbiotic fecal microbiome, or dextran sodium sulfate administration. We identified an immune signature of αCTLA-4-mediated irAEs, including colonic neutrophil accumulation and s","dates":{"release":"2023-01-01T00:00:00Z","publication":"2023 Feb","modification":"2025-04-22T07:47:30.37Z","creation":"2025-04-05T22:15:53.069Z"},"accession":"S-EPMC9664499","cross_references":{"pubmed":["36367776"],"doi":["10.1084/jem.20221333"]}}