T cell anergy, exhaustion, senescence, and stemness in the tumor microenvironment

Curr Opin Immunol. 2013 Apr;25(2):214-21. doi: 10.1016/j.coi.2012.12.003. Epub 2013 Jan 6.


Human tumors progress despite the presence of tumor associated antigen (TAA)-specific T cells. Many different molecular and cellular mechanisms contribute to the failure of T cells to eradicate the tumor. These include immune suppressive networks that impair ongoing T cell function and enable tumor escape. Recent studies have started to reveal the nature of effector T cells in the tumor microenvironment. In this article we discuss T cell anergy, exhaustion, senescence, and stemness, and review the phenotype of dysfunctional T cell subsets and the underlying molecular mechanisms in the tumor microenvironments. We suggest that targeting T cell dysfunctional mechanisms and introducing/promoting T cell stemness are important approaches to treat patients with cancer.

Publication types

  • Review

MeSH terms

  • Animals
  • Cellular Senescence*
  • Clonal Anergy / immunology*
  • Humans
  • Neoplasms / immunology*
  • Neoplasms / therapy
  • Stem Cells* / immunology
  • T-Lymphocytes / cytology
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / pathology*
  • Tumor Microenvironment / immunology*