Wang, Zhikai, Moresco, Philip, Yan, Ran, Li, Jiayun, Gao, Ya, Biasci, Daniele, Yao, Min, Pearson, Jordan, Hechtman, Jaclyn F, Janowitz, Tobias, Zaidi, Raza M, Weiss, Matthew J, Fearon, Douglas T (January 2022) Carcinomas assemble a filamentous CXCL12-keratin-19 coating that suppresses T cell-mediated immune attack. Proceedings of the National Academy of Sciences of USA, 119 (4). e2119463119-e2119463119. ISSN 0027-8424
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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 coating, were infiltrated with activated CD8+ T cells, and growth was suppressed with anti-PD-1 antibody treatment. Thus, carcinomas assemble a CXCL12-KRT19 coating to evade cancer immune attack.
Item Type: | Paper |
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Subjects: | organs, tissues, organelles, cell types and functions > cell types and functions > cell types > T cells organs, tissues, organelles, cell types and functions > cell types and functions > cell types > T cells organs, tissues, organelles, cell types and functions > cell types and functions > cell types > T cells diseases & disorders > cancer > cancer types > breast cancer diseases & disorders > cancer > cancer types > colorectal diseases & disorders > cancer > drugs and therapies > Immunotherapy diseases & disorders > cancer > cancer types > pancreatic cancer |
CSHL Authors: | |
Communities: | CSHL labs > Fearon lab CSHL labs > Janowitz lab |
SWORD Depositor: | CSHL Elements |
Depositing User: | CSHL Elements |
Date: | 25 January 2022 |
Date Deposited: | 26 Jan 2022 16:34 |
Last Modified: | 10 Feb 2022 20:31 |
PMCID: | PMC8794816 |
URI: | https://repository.cshl.edu/id/eprint/40501 |
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