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

Nat Rev Cancer. 2020 Apr;20(4):218-232. doi: 10.1038/s41568-019-0235-4. Epub 2020 Feb 5.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Antigens, Neoplasm / immunology
  • Biomarkers
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / metabolism*
  • CD8-Positive T-Lymphocytes / pathology
  • Disease Susceptibility
  • Humans
  • Lymphocyte Activation / immunology
  • Lymphocytes, Tumor-Infiltrating / immunology*
  • Lymphocytes, Tumor-Infiltrating / metabolism*
  • Lymphocytes, Tumor-Infiltrating / pathology
  • Neoplasms / etiology*
  • Neoplasms / metabolism*
  • Neoplasms / pathology
  • Prognosis
  • Single-Cell Analysis
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / metabolism
  • T-Lymphocyte Subsets / pathology
  • Tumor Microenvironment


  • Antigens, Neoplasm
  • Biomarkers