Carcinomas assemble a filamentous CXCL12–keratin-19 coating that suppresses T cell–mediated immune attack-Reference-Cited by-同舟云学术

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

Published:2022-01-19 Issue:4 Volume:119 Page:
ISSN:0027-8424
Container-title:Proceedings of the National Academy of Sciences
language:en
Short-container-title:Proc. Natl. Acad. Sci. U.S.A.

Author:

Wang Zhikai¹^ORCID,Moresco Philip¹²³,Yan Ran¹⁴,Li Jiayun¹,Gao Ya¹,Biasci Daniele⁵,Yao Min¹,Pearson Jordan¹²³,Hechtman Jaclyn F.⁶,Janowitz Tobias¹⁷^ORCID,Zaidi Raza M.⁷⁸,Weiss Matthew J.⁷,Fearon Douglas T.¹⁹^ORCID

Affiliation:

1. Cancer Center, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724

2. Graduate Program in Genetics, Stony Brook University, Stony Brook, NY 11794

3. Medical Scientist Training Program, Stony Brook University Renaissance School of Medicine, Stony Brook University, Stony Brook, NY 11794

4. School of Biological Sciences, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724

5. Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge CB2 0RE, United Kingdom

6. Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY 10065

7. Northwell Health Cancer Institute, Northwell Health, Lake Success, NY 11042

8. Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Northwell Health, Hempstead, NY 11549

9. Meyer Cancer Center, Weill Cornell Medicine, New York, NY 10065

Abstract

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.

Funder

Lustgarten Foundation

Thompson Family Foundation

Cedar Hill Foundation

Publisher

Proceedings of the National Academy of Sciences

Subject

Multidisciplinary

Link

https://pnas.org/doi/pdf/10.1073/pnas.2119463119

Reference26 articles.

1. PD-1 and Its Ligands in Tolerance and Immunity