Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2018 Nov 22;10(1):87.
doi: 10.1186/s13073-018-0598-2.

Acquired mechanisms of immune escape in cancer following immunotherapy

J Bryan Iorgulescu  1   2   3   4 , David Braun  1   2   4 , Giacomo Oliveira  1   2 , Derin B Keskin  1   2   5 , Catherine J Wu  6   7   8
Affiliations

Acquired mechanisms of immune escape in cancer following immunotherapy

J Bryan Iorgulescu et al. Genome Med. .

Abstract

Immunotherapy has revolutionized the management of numerous cancers; however, a substantial proportion that initially respond subsequently acquire means of immune escape and relapse. Analysis of recent clinical trials permits us to preliminarily understand how immunotherapies exert evolutionary pressures: selecting cancer subclones deficient in antigenicity and/or immunogenicity, thereby facilitating immune escape.

PubMed Disclaimer

Conflict of interest statement

Competing interests

CJW reports being a co-founder of Neon Therapeutics and a member of its scientific advisory board. The remaining authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
The great escape: acquired mechanisms of immune evasion in cancer. Multiple immunotherapeutic approaches have potently targeted T-cell responses (T) against cancer cells (C) in the clinical setting (1); however, a substantial subset of initial responders acquire novel immunogenomic means of immune escape and relapse. From clinical investigations, the most common acquired mechanisms of immune escape appear to be (2) deficits in antigen presentation machinery, (3) loss of antigenicity, and/or (4) loss of immunogenicity—including by exploiting bypass immune checkpoint pathways
See this image and copyright information in PMC

References

    1. Schreiber RD. Tumor immunology. Adv Immunol. 2016;130:2–318.
    1. Zaretsky JM, Garcia-Diaz A, Shin DS, Escuin-Ordinas H, Hugo W, Hu-Lieskovan S, et al. Mutations associated with acquired resistance to PD-1 blockade in melanoma. N Engl J Med. 2016;375:819–829. doi: 10.1056/NEJMoa1604958. - DOI - PMC - PubMed
    1. Sade-Feldman M, Jiao YJ, Chen JH, Rooney MS, Barzily-Rokni M, Eliane J-P, et al. Resistance to checkpoint blockade therapy through inactivation of antigen presentation. Nat Commun. 2017;8:1136. doi: 10.1038/s41467-017-01062-w. - DOI - PMC - PubMed
    1. Sotillo E, Barrett DM, Black KL, Bagashev A, Oldridge D, Wu G, et al. Convergence of acquired mutations and alternative splicing of CD19 enables resistance to CART-19 immunotherapy. Cancer Discov. 2015;5:1282–1295. doi: 10.1158/2159-8290.CD-15-1020. - DOI - PMC - PubMed
    1. Mehta A, Kim YJ, Robert L, Tsoi J, Comin-Anduix B, Berent-Maoz B, et al. Immunotherapy resistance by inflammation-induced dedifferentiation. Cancer Discov. 2018;8:935–943. doi: 10.1158/2159-8290.CD-17-1178. - DOI - PMC - PubMed

Publication types

LinkOut - more resources