Is autoimmunity the Achilles' heel of cancer immunotherapy?

A Corrigendum to this article was published on 01 August 2017

This article has been updated (view changelog)

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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Figure 1: Examples of autoimmune and other immune-related adverse effects associated with cancer immunotherapy.

Kim Caesar/Springer Nature

Figure 2: CTLA-4 and PD-1 checkpoint blockade affects T cells at different stages of differentiation and at different anatomical locations.

Kim Caesar/Springer Nature

Figure 3: Potential mechanism of epitope spreading leading to autoimmunity.

Kim Caesar/Springer Nature

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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Correspondence to Carl H June.

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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.

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June, C., Warshauer, J. & Bluestone, J. Is autoimmunity the Achilles' heel of cancer immunotherapy?. Nat Med 23, 540–547 (2017). https://doi.org/10.1038/nm.4321

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