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

In this Review, the authors describe how dysregulated protein translation in cancer cells is an important source of tumour-specific peptides for immunosurveillance and how MHC class I antigen-processing and presentation pathways are manipulated by tumours for immunoevasion - information that will inform cancer immunotherapy approaches. 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.

Automated summary

In this review, the authors discuss the impact of dysregulated protein translation in cancer cells on immunosurveillance, as well as how tumors manipulate antigen-processing pathways for immune evasion. Additionally, they highlight two limiting factors in the application of CD8(+)T cell immunotherapies.