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CD8+ T cell states in human cancer: insights from single-cell analysis

Nature Reviews Cancer volume 20, pages 218–232 (2020)Cite this article

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Abstract

The T cell infiltrates that are formed in human cancers are a modifier of natural disease progression and also determine the probability of clinical response to cancer immunotherapies. Recent technological advances that allow the single-cell analysis of phenotypic and transcriptional states have revealed a vast heterogeneity of intratumoural T cell states, both within and between patients, and the observation of this heterogeneity makes it critical to understand the relationship between individual T cell states and therapy response. This Review covers our current knowledge of the T cell states that are present in human tumours and the role that different T cell populations have been hypothesized to play within the tumour microenvironment, with a particular focus on CD8+ T cells. The three key models that are discussed herein are as follows: (1) the dysfunction of T cells in human cancer is associated with a change in T cell functionality rather than inactivity; (2) antigen recognition in the tumour microenvironment is an important driver of T cell dysfunctionality and the presence of dysfunctional T cells can hence be used as a proxy for the presence of a tumour-reactive T cell compartment; (3) a less dysfunctional population of tumour-reactive T cells may be required to drive a durable response to T cell immune checkpoint blockade.

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Fig. 1: Model of intratumoural CD8+ T cell states.
Fig. 2: Model for the development of CD8+ T cell dysfunction and the effect of PD1 blockade.
Fig. 3: Hallmarks of intratumoural tumour-reactive CD8+ T cells.

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Acknowledgements

The authors thank Y. Lubling and M. Logtenberg for input and insightful discussions. This work was supported by ERC AdG SENSIT to T.N.S. and the Dutch Cancer Society Bas Mulder Award to D.S.T.

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  1. Division of Molecular Oncology and Immunology, Oncode Institute, Netherlands Cancer Institute, Amsterdam, Netherlands

    Anne M. van der Leun, Daniela S. Thommen & Ton N. Schumacher

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A.M.v.d.L researched data for the article. A.M.v.d.L, D.S.T. and T.N.S. jointly discussed data and co-wrote the article.

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Correspondence to Ton N. Schumacher.

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Glossary

Tumour-specific T cell reactivity

The capacity of a T cell to recognize tumour cells, regardless of its ability to perform effector function.

Single-cell RNA sequencing

Gene expression profiling method that allows unbiased transcriptome analysis of individual cells.

Clonotype

The unique T cell receptor (TCR) sequence formed by both the TCR α-chain and the TCR β-chain.

Predictive biomarkers

Certain measurements (for example, T cell count or expression level of a marker gene) to make a risk estimate of the response of a patient to therapy.

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van der Leun, A.M., Thommen, D.S. & Schumacher, T.N. CD8+ T cell states in human cancer: insights from single-cell analysis. Nat Rev Cancer 20, 218–232 (2020). https://doi.org/10.1038/s41568-019-0235-4

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