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

Proc Natl Acad Sci U S A. 2022 Jan 25;119(4):e2119463119. doi: 10.1073/pnas.2119463119.


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.

Keywords: CXCL12; T cells; cancer immunology; keratin-19; transglutaminase-2.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Breast Neoplasms
  • Carcinoma / etiology*
  • Carcinoma / metabolism*
  • Carcinoma / pathology
  • Cell Line, Tumor
  • Chemokine CXCL12 / chemistry
  • Chemokine CXCL12 / metabolism*
  • Cytotoxicity, Immunologic*
  • Female
  • Humans
  • Keratin-19 / chemistry
  • Keratin-19 / metabolism*
  • Male
  • Mice
  • Microsatellite Repeats
  • Pancreatic Neoplasms
  • Protein Binding
  • Protein Multimerization
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism*


  • Chemokine CXCL12
  • Keratin-19