Open AccessCarcinomas assemble a filamentous CXCL12–keratin-19 coating that suppresses T cell–mediated immune attack
Author(s) -
Zhikai Wang,
Philip Moresco,
Ran Yan,
Jiayun Li,
Ya Gao,
Daniele Biasci,
Min Yao,
Jordan Pearson,
Jaclyn F. Hechtman,
Tobias Janowitz,
Raza Zaidi,
Matthew J. Weiss,
Douglas T. Fearon
Publication year - 2022
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2119463119
Subject(s) - keratin , immune system , chemistry , microbiology and biotechnology , segmented filamentous bacteria , biology , cancer research , immunology , genetics , sewage treatment , activated sludge , engineering , waste management
Significance Carcinomas resist immunotherapy because T cells are absent from nests of cancer cells. The chemokine/chemokine receptor system, which regulates the migration of immune cells, is a candidate for this impaired intratumoral accumulation of T cells. Cancer cells in human pancreatic, colorectal, and breast cancers are coated with the chemokine CXCL12 in the form of covalent heterodimers with keratin-19. This CXCL12 coating was investigated using a mouse model of pancreatic cancer that replicates the immunological characteristics of human cancer. Mouse pancreatic cancer cells without the CXCL12 coating formed tumors that did not exclude T cells and responded to anti–PD-1 antibody treatment. Thus, the ability of cancer cells to coat themselves with CXCL12 may contribute to resistance to immunotherapy.