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  • Perspective
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Bystander T cells in cancer immunology and therapy

Nature Cancer volume 3, pages 143–155 (2022)Cite this article

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Abstract

Cancer-specific T cells are required for effective anti-cancer immunity and have a central role in cancer immunotherapy. However, emerging evidence suggests that only a small fraction of tumor-infiltrating T cells are cancer specific, and T cells that recognize cancer-unrelated antigens (so-called ‘bystanders’) are abundant. Although the role of cancer-specific T cells in anti-cancer immunity has been well established, the implications of bystander T cells in tumors are only beginning to be understood. It is becoming increasingly clear that bystander T cells are not a homogeneous group of cells but, instead, they differ in their specificities, their activation states and effector functions. In this Perspective, we discuss recent studies of bystander T cells in tumors, including experimental and computational approaches that enable their identification and functional analysis and viewpoints on how these insights could be used to develop new therapeutic approaches for cancer immunotherapy.

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Fig. 1: Characteristics of tumor-infiltrating T cells.
Fig. 2: Therapeutic approaches that leverage bystander TILs.

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Data sharing is not applicable to this article as no datasets were generated or analyzed for this study.

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Acknowledgements

A.T.S. was supported by the National Institutes of Health grant K08CA230188, a Technology Impact Award from the Cancer Research Institute and a Career Award for Medical Scientists from the Burroughs Wellcome Fund. A.T.S. and S.L.M. were supported by the Parker Institute for Cancer Immunotherapy.

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Authors and Affiliations

  1. Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA

    Stefanie L. Meier & Ansuman T. Satpathy

  2. Parker Institute for Cancer Immunotherapy, San Francisco, CA, USA

    Stefanie L. Meier & Ansuman T. Satpathy

  3. Immunai, New York, NY, USA

    Daniel K. Wells

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  1. Stefanie L. Meier
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  2. Ansuman T. Satpathy
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  3. Daniel K. Wells
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Correspondence to Daniel K. Wells.

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Competing interests

A.T.S. is a scientific cofounder of Immunai and Cartography Biosciences and receives research funding from Merck Research Laboratories and Allogene Therapeutics. D.K.W. is a scientific cofounder and employee of Immunai and has received consulting fees from Rubius Therapeutics, Illumina and DeepMind. S.L.M. has no conflicts of interest to declare.

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Meier, S.L., Satpathy, A.T. & Wells, D.K. Bystander T cells in cancer immunology and therapy. Nat Cancer 3, 143–155 (2022). https://doi.org/10.1038/s43018-022-00335-8

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