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

Authors: Zhikai Wang, Philip Moresco, Ran Yan, Jiayun Li, Ya Gao, Daniele Biasci, Min Yao, Jordan Pearson, Jaclyn F. Hechtman, Tobias Janowitz, Raza M. Zaidi, Matthew J. Weiss, Douglas T. Fearon - Proceedings of the National Academy of Sciences, PNAS 2022 cited by 70

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.