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

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

This article has been updated

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.

Change history

  • 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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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 (2020). https://doi.org/10.1038/s41577-020-0390-6

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