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Not-so-opposite ends of the spectrum: CD8+ T cell dysfunction across chronic infection, cancer and autoimmunity

Nature Immunology volume 22, pages 809–819 (2021)Cite this article

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Abstract

CD8+ T cells are critical mediators of cytotoxic effector function in infection, cancer and autoimmunity. In cancer and chronic viral infection, CD8+ T cells undergo a progressive loss of cytokine production and cytotoxicity, a state termed T cell exhaustion. In autoimmunity, autoreactive CD8+ T cells retain the capacity to effectively mediate the destruction of host tissues. Although the clinical outcome differs in each context, CD8+ T cells are chronically exposed to antigen in all three. These chronically stimulated CD8+ T cells share some common phenotypic features, as well as transcriptional and epigenetic programming, across disease contexts. A better understanding of these CD8+ T cell states may reveal novel strategies to augment clearance of chronic viral infection and cancer and to mitigate self-reactivity leading to tissue damage in autoimmunity.

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Fig. 1: ‘Opposite ends of the spectrum’ framework of CD8+ T cells in autoimmunity versus chronic viral infection and cancer.
Fig. 2: Temporal changes of CD8+ T cells in cancer, chronic viral infection and autoimmunity.

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Acknowledgements

A.H.S. received funding from the National Institutes of Health, grants P01 AI56299, P01AI039671 and P01 AI108545. S.A.W. received funding from the National Institutes of Health, award T32GM007753.

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  1. These authors contributed equally: Jenna L. Collier, Sarah A. Weiss.

Authors and Affiliations

  1. Department of Immunology, Blavatnik Institute, Harvard Medical School, Boston, MA, USA

    Jenna L. Collier, Sarah A. Weiss, Kristen E. Pauken, Debattama R. Sen & Arlene H. Sharpe

  2. Evergrande Center for Immunologic Diseases, Harvard Medical School and Brigham and Women’s Hospital, Boston, MA, USA

    Jenna L. Collier, Sarah A. Weiss, Kristen E. Pauken & Arlene H. Sharpe

  3. Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA

    Sarah A. Weiss

  4. Broad Institute of MIT and Harvard, Cambridge, MA, USA

    Sarah A. Weiss & Arlene H. Sharpe

  5. Center for Cancer Research, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA

    Debattama R. Sen

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J.L.C., S.A.W., K.E.P., D.R.S. and A.H.S. conceived and wrote the manuscript.

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Correspondence to Arlene H. Sharpe.

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Competing interests

A.H.S. has patents/pending royalties on the PD-1 pathway from Roche and Novartis. A.H.S. is on advisory boards for Surface Oncology, Elstar, SQZ Biotechnologies, Elpiscience, Selecta, Bicara and Monopteros, GlaxoSmithKline and Janssen, and consults for Novartis. A.H.S. has received research funding from Novartis, Roche, UCB, Ipsen, Quark, Merck and AbbVie unrelated to this project.

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Peer review information Nature Immunology thanks the anonymous reviewers for their contribution to the peer review of this work. Jamie D. K. Wilson was the primary editor on this article and managed its editorial process and peer review in collaboration with the rest of the editorial team.

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Collier, J.L., Weiss, S.A., Pauken, K.E. et al. Not-so-opposite ends of the spectrum: CD8+ T cell dysfunction across chronic infection, cancer and autoimmunity. Nat Immunol 22, 809–819 (2021). https://doi.org/10.1038/s41590-021-00949-7

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