{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Wang Z"],"funding":["Cedar Hill Foundation","Lustgarten Foundation","NCI NIH HHS","Thompson Family Foundation","NIGMS NIH HHS"],"pagination":["e2119463119"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC8794816"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["119(4)"],"pubmed_abstract":["Cancer immunotherapy frequently fails because most carcinomas have few T cells, suggesting that cancers can suppress T cell infiltration. Here, we show that cancer cells of human pancreatic ductal adenocarcinoma (PDA), colorectal cancer, and breast cancer are coated with transglutaminase-2 (TGM2)-dependent covalent CXCL12-keratin-19 (KRT19) heterodimers that are organized as filamentous networks. Since a dimeric form of CXCL12 suppresses the motility of human T cells, we determined whether this polymeric CXCL12-KRT19 coating mediated T cell exclusion. Mouse tumors containing control PDA cells exhibited the CXCL12-KRT19 coating, excluded T cells, and did not respond to treatment with anti-PD-1 antibody. Tumors containing PDA cells not expressing either KRT19 or TGM2 lacked the CXCL12-KRT19 "],"journal":["Proceedings of the National Academy of Sciences of the United States of America"],"pubmed_title":["Carcinomas assemble a filamentous CXCL12-keratin-19 coating that suppresses T cell-mediated immune attack."],"pmcid":["PMC8794816"],"funding_grant_id":["Distinguished Scholar Award","F30 CA265134","No reference number","P30 CA008748","T32 GM008444","P30 CA045508"],"pubmed_authors":["Moresco P","Fearon DT","Li J","Biasci D","Yao M","Janowitz T","Yan R","Hechtman JF","Pearson J","Zaidi RM","Weiss MJ","Gao Y","Wang Z"],"additional_accession":[]},"is_claimable":false,"name":"Carcinomas assemble a filamentous CXCL12-keratin-19 coating that suppresses T cell-mediated immune attack.","description":"Cancer immunotherapy frequently fails because most carcinomas have few T cells, suggesting that cancers can suppress T cell infiltration. Here, we show that cancer cells of human pancreatic ductal adenocarcinoma (PDA), colorectal cancer, and breast cancer are coated with transglutaminase-2 (TGM2)-dependent covalent CXCL12-keratin-19 (KRT19) heterodimers that are organized as filamentous networks. Since a dimeric form of CXCL12 suppresses the motility of human T cells, we determined whether this polymeric CXCL12-KRT19 coating mediated T cell exclusion. Mouse tumors containing control PDA cells exhibited the CXCL12-KRT19 coating, excluded T cells, and did not respond to treatment with anti-PD-1 antibody. Tumors containing PDA cells not expressing either KRT19 or TGM2 lacked the CXCL12-KRT19 ","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Jan","modification":"2025-04-22T15:23:08.212Z","creation":"2025-04-06T01:19:47.568Z"},"accession":"S-EPMC8794816","cross_references":{"pubmed":["35046049"],"doi":["10.1073/pnas.2119463119"]}}