Perspective | Published:

Is autoimmunity the Achilles' heel of cancer immunotherapy?

Nature Medicine volume 23, pages 540547 (2017) | Download Citation

  • A Corrigendum to this article was published on 04 August 2017

This article has been updated

Abstract

The emergence of immuno-oncology as the first broadly successful strategy for metastatic cancer will require clinicians to integrate this new pillar of medicine with chemotherapy, radiation, and targeted small-molecule compounds. Of equal importance is gaining an understanding of the limitations and toxicities of immunotherapy. Immunotherapy was initially perceived to be a relatively less toxic approach to cancer treatment than other available therapies—and surely it is, when compared to those. However, as the use of immunotherapy becomes more common, especially as first- and second-line treatments, immunotoxicity and autoimmunity are emerging as the Achilles' heel of immunotherapy. In this Perspective, we discuss evidence that the occurrence of immunotoxicity bodes well for the patient, and describe mechanisms that might be related to the induction of autoimmunity. We then explore approaches to limit immunotoxicity, and discuss the future directions of research and reporting that are needed to diminish it.

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Change history

  • 05 May 2017

    In the version of this article published in print, Jeffrey A Bluestone was missing an affiliation. His affiliation information has been changed to include the Parker Institute for Cancer Immunotherapy in San Francisco, California. Accordingly, the affiliation information for Carl H June has been updated to distinguish the Parker Institute from the University of Pennsylvania; these are now two separate affiliations. All affiliation numbers have been revised. The error did not appear in the HTML and PDF versions of the article.

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Acknowledgements

C.H.J. and J.A.B. are members of the Parker Institute for Cancer Immunotherapy, which supported this study and which supports the University of Pennsylvania and University of San Francisco Cancer Immunotherapy Programs. The authors thank B. Levine for constructive comments, and the authors apologize to colleagues for work that we are unable to cite owing to space constraints.

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Affiliations

  1. Parker Institute for Cancer Immunotherapy, San Francisco, California, USA.

    • Carl H June
    •  & Jeffrey A Bluestone
  2. Center for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

    • Carl H June
  3. Endocrine Division, Department of Medicine, University of California, San Francisco, San Francisco, California, USA.

    • Jeremy T Warshauer
  4. Diabetes Center, University of California, San Francisco, San Francisco, California, USA.

    • Jeffrey A Bluestone

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Competing interests

C.H.J. is a recipient of a Novartis-sponsored research grant #2161, founder of Tmunity Therapeutics and a member of the Scientific Advisory Boards of Celldex Therapeutics and Immune Design. J.A.B. is an advisor and grant recipient of Juno Therapeutics; a member of the Scientific Advisory Boards of Arcus, FLXBio and Pfizer.

Corresponding author

Correspondence to Carl H June.

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https://doi.org/10.1038/nm.4321

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