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A few good peptides: MHC class I-based cancer immunosurveillance and immunoevasion

Nature Reviews Immunology volume 21, pages 116–128 (2021)Cite this article

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An Author Correction to this article was published on 01 September 2020

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Abstract

The remarkable success of immune checkpoint inhibitors demonstrates the potential of tumour-specific CD8+ T cells to prevent and treat cancer. Although the number of lives saved by immunotherapy mounts, only a relatively small fraction of patients are cured. Here, we review two of the factors that limit the application of CD8+ T cell immunotherapies: difficulties in identifying tumour-specific peptides presented by MHC class I molecules and the ability of tumour cells to impair antigen presentation as they evolve under T cell selection. We describe recent advances in understanding how peptides are generated from non-canonical translation of defective ribosomal products, relate this to the dysregulated translation that is a feature of carcinogenesis and propose dysregulated translation as an important new source of tumour-specific peptides. We discuss how the synthesis and function of components of the antigen-processing and presentation pathway, including the recently described immunoribosome, are manipulated by tumours for immunoevasion and point to common druggable targets that may enhance immunotherapy.

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Fig. 1: Overview of MHC class I biogenesis antigen-processing and presentation machinery.
Fig. 2: Potential sources of tumour antigens as targets for immunosurveillance and targeted cell immunotherapy.
Fig. 3: Mechanisms of cancer cell immunoevasion.

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  • 01 September 2020

    An amendment to this paper has been published and can be accessed via a link at the top of the paper.

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Acknowledgements

The authors are supported by the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, and a FLEX project grant from the National Cancer Institute Division of Intramural Research. They thank M. Gumina for careful editing of the manuscript.

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  1. Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, US National Institutes of Health, Bethesda, MD, USA

    Devin Dersh, Jaroslav Hollý & Jonathan W. Yewdell

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Glossary

Law of mass action

The principle that processes are proportional to the concentrations of the participants.

Phase separation

The creation of distinct compartments from a homogeneous mixture.

Negative selection

Also known as clonal deletion. The process by which developing lymphocytes expressing potentially autoreactive antigen-specific receptors are induced to undergo apoptosis in the thymus.

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Dersh, D., Hollý, J. & Yewdell, J.W. A few good peptides: MHC class I-based cancer immunosurveillance and immunoevasion. Nat Rev Immunol 21, 116–128 (2021). https://doi.org/10.1038/s41577-020-0390-6

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