CD8 T Cell Exhaustion During Chronic Viral Infection and Cancer.

By Laura M. McLane, Mohamed S. Abdel-Hakeem, E. Wherry. Annual Review of Immunology, 2019

1,686 citations recorded by the source corpus.

Exhausted CD8 T (Tex) cells are a distinct cell lineage that arise during chronic infections and cancers in animal models and humans. Tex cells are characterized by progressive loss of effector functions, high and sustained inhibitory receptor expression, metabolic dysregulation, poor memory recall and homeostatic self-renewal, and distinct transcriptional and epigenetic programs. The ability to reinvigorate Tex cells through inhibitory receptor blockade, such as αPD-1, highlights the therapeutic potential of targeting this population. Emerging insights into the mechanisms of exhaustion are informing immunotherapies for cancer and chronic infections. However, like other immune cells, Tex cells are heterogeneous and include progenitor and terminal subsets with unique characteristics and responses to checkpoint blockade. Here, we review our current understanding of Tex cell biology, including the developmental paths, transcriptional and epigenetic features, and cell intrinsic and extrinsic factors contributing to exhaustion and how this knowledge may inform therapeutic targeting of Tex cells in chronic infections, autoimmunity, and cancer.

Subfields: Immunology, Oncology

View Paper: https://www.semanticscholar.org/paper/0239372203803540e7400053a3e0a225630a8d9f

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Immunology

1. Anjana Rao
2. P. Hogan
3. E. Wherry
4. Li-Fan Lu
5. Rafi Ahmed
6. A. Schietinger
7. P. Greenberg
8. J. Snyder-Cappione

In Oncology

1. Anjana Rao
2. E. Wherry
3. A. Schietinger
4. P. Greenberg
5. J. Snyder-Cappione
6. Anna C. Belkina

Citations in the corpus

• TOX and TOX2 transcription factors cooperate with NR4A transcription factors to impose CD8+ T cell exhaustion (2019, background): “apparently because the CAR T cells become exhausted, much like T cells responsive to standard peptide/major histocompatibility complex ligands (5, 6).”
• Deep immune profiling of COVID-19 patients reveals distinct immunotypes with therapeutic implications (2020, background): “T cell exhaustion (12, 13) and increased inhibitory receptor expression on peripheral T cells have also been reported (7, 14), though these inhibitory receptors are also increased after T cell activation (15).”
• Reduction and Functional Exhaustion of T Cells in Patients With Coronavirus Disease 2019 (COVID-19) (2020, neutral): “32 By FACs analysis, we found that both CD8 + T cells and CD4 + T cells have higher levels of PD-1 in virus infected patients, particularly when derived from ICU patients.”