Carcinomas assemble a filamentous CXCL12-keratin-19 coating that suppresses T cell-mediated immune attack

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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URL: https://www.ncbi.nlm.nih.gov/pubmed/35046049
DOI: 10.1073/pnas.2119463119

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
Subjects: diseases & disorders > cancer
diseases & disorders
diseases & disorders > neoplasms
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
organism description > animal
diseases & disorders > cancer > cancer types > breast cancer
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > cell line
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > cell line
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > cell line
organs, tissues, organelles, cell types and functions > cell types and functions > cell types
organs, tissues, organelles, cell types and functions > cell types and functions > cell types
organs, tissues, organelles, cell types and functions > cell types and functions > cell types
organs, tissues, organelles, cell types and functions > cell types and functions
diseases & disorders > inflammation > chemokines
diseases & disorders > cancer > cancer types > colorectal
diseases & disorders > cancer > drugs and therapies
organism description > animal > gender > female
organism description > animal > gender
diseases & disorders > cancer > drugs and therapies > Immunotherapy
diseases & disorders > inflammation
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > lymphocyte
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > lymphocyte
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > lymphocyte
organism description > animal > mammal
organism description > animal > mammal > rodent > mouse
organs, tissues, organelles, cell types and functions
diseases & disorders > cancer > cancer types > pancreatic cancer
organism description > animal > mammal > rodent
diseases & disorders > cancer > cancer types
CSHL Authors:
Communities: CSHL Cancer Center Program
CSHL Cancer Center Shared Resources > Animal Services
CSHL Cancer Center Shared Resources > Animal Tissue and Imaging Service
CSHL Cancer Center Shared Resources > Flow Cytometry Service
CSHL Cancer Center Shared Resources > Histology Service
CSHL Cancer Center Shared Resources > Microscopy Service
CSHL labs > Fearon lab
CSHL labs > Janowitz lab
School of Biological Sciences > Publications
SWORD Depositor: CSHL Elements
Depositing User: CSHL Elements
Date: 25 January 2022
Date Deposited: 26 Jan 2022 16:34
Last Modified: 29 Feb 2024 19:26
PMCID: PMC8794816
URI: https://repository.cshl.edu/id/eprint/40501

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