Mechanisms of intrinsic tumor resistance to immunotherapy

John Rieth, Subree Subramanian

Research output: Contribution to journalReview articlepeer-review

59 Scopus citations


An increased understanding of the interactions between the immune system and tumors has opened the door to immunotherapy for cancer patients. Despite some success with checkpoint inhibitors including ipilimumab, pembrolizumab, and nivolumab, most cancer patients remain unresponsive to such immunotherapy, likely due to intrinsic tumor resistance. The mechanisms most likely involve reducing the quantity and/or quality of antitumor lymphocytes, which ultimately are driven by any number of developments: tumor mutations and adaptations, reduced neoantigen generation or expression, indoleamine 2,3-dioxygenase (IDO) overexpression, loss of phosphatase and tensin homologue (PTEN) expression, and overexpression of the Wnt–β-catenin pathway. Current work in immunotherapy continues to identify various tumor resistance mechanisms; future work is needed to develop adjuvant treatments that target those mechanisms, in order to improve the efficacy of immunotherapy and to expand its scope.

Original languageEnglish (US)
Article number1393
JournalInternational journal of molecular sciences
Issue number5
StatePublished - May 2 2018

Bibliographical note

Funding Information:
Acknowledgments: Because of space restrictions, we cannot cite the many significant contributions made by numerous researchers and laboratories in this important, rapidly progressing field. S.S. is supported by a research grant from the National Cancer Institute (NCI) of the National Institutes of Health (NIH), grant number R03CA219129, and from the Mezin-Koats Colon Cancer Research Fund. We thank Mary Knatterud for assisting in manuscript preparation.

Publisher Copyright:
© 2018 by the authors. Licensee MDPI, Basel, Switzerland.


  • Cancer immunotherapy
  • Oncogenes
  • Resistance
  • Signaling pathways


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