Acquired resistance to immune checkpoint blockade therapies

Xianda Zhao, Dechen Wangmo, Matthew Robertson, Subbaya Subramanian

Research output: Contribution to journalReview articlepeer-review

9 Scopus citations


Immune checkpoint blockade therapy (ICBT) has revolutionized the treatment and management of numerous cancers, yet a substantial proportion of patients who initially respond to ICBT subsequently develop resistance. Comprehensive genomic analysis of samples from recent clinical trials and pre-clinical investigation in mouse models of cancer provide insight into how tumors evade ICBT after an initial response to treatment. Here, we summarize our current knowledge on the development of acquired ICBT resistance, by examining the mechanisms related to tumor-intrinsic properties, T-cell function, and tumor-immune cell interactions. We discuss current and future management of ICBT resistance, and consider crucial questions remaining in this field of acquired resistance to immune checkpoint blockade therapies.

Original languageEnglish (US)
Article number1161
Issue number5
StatePublished - May 2020

Bibliographical note

Funding Information:
S.S. is supported by research grants funded by the NIH R03CA219129 and Masonic Cancer Center ChainBreaker Fund and Mezin Koats and Minnesota colon cancer research funds and the Department of Surgery, University of Minnesota Research funds. We thank William Shawn Morris and Isabella Ramirez for assisting in manuscript preparation. Because of space restrictions, we cannot cite many other significant contributions made by numerous researchers and laboratories in this potentially important and rapidly progressing field.

Publisher Copyright:
© 2020 by the authors. Licensee MDPI, Basel, Switzerland.


  • Acquired resistance
  • CTLA-4
  • Immune checkpoint blockade
  • Immune response
  • PD-1
  • T cells
  • Tumor immunology


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