Molecular and cellular insights into T cell exhaustion
By J. Wherry, M. Kurachi. Nature reviews. Immunology, 2015
4,114 citations recorded by the source corpus.
In chronic infections and cancer, T cells are exposed to persistent antigen and/or inflammatory signals. This scenario is often associated with the deterioration of T cell function: a state called 'exhaustion'. Exhausted T cells lose robust effector functions, express multiple inhibitory receptors and are defined by an altered transcriptional programme. T cell exhaustion is often associated with inefficient control of persisting infections and tumours, but revitalization of exhausted T cells can reinvigorate immunity. Here, we review recent advances that provide a clearer molecular understanding of T cell exhaustion and reveal new therapeutic targets for persisting infections and cancer.
Subfields: Immunology, Oncology
View Paper: https://www.semanticscholar.org/paper/bace03ef4ede2ffa83a113ef55cf497d079dc3e4
How researchers see this paper
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In Immunology
- S. Kaech
- E. Wherry
- Ton N. Schumacher
- Kristen E. Pauken
- Michael D. Buck
- V. Kuchroo
- R. Sowell
- A. Anderson
In Oncology
- Ton N. Schumacher
- Kristen E. Pauken
- S. Kaech
- Laura M. McLane
- V. Kuchroo
- M. Kurachi
- Erika L. Pearce
- Michael D. Buck
Citations in the corpus
- T cell costimulatory receptor CD28 is a primary target for PD-1–mediated inhibition (2016, background): “Thus, during chronic viral infection, T cells become progressively “exhausted”, reflecting a homeostatic negative feedback loop due to increased expression of PD-1 and PD-L1(7-9).”
- Landscape of Infiltrating T Cells in Liver Cancer Revealed by Single-Cell Sequencing. (2017, positive): “It has been recognized previously that T cells within the tumor microenvironment are prone to either exhaustion or Treg suppression, thus preventing such CD8 cells from eliciting sufficient T cell-mediated killing of tumor cells (Wherry and Kurachi, 2015).”
- Immunosenescence and Inflamm-Aging As Two Sides of the Same Coin: Friends or Foes? (2018, background): “One additional consequence of chronic stimulation is the phenomenon of exhaustion, characterized by the emergence of inhibitory receptors, such as PD-1, CTLA-4, and many others (75).”