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CD8 T Cell Exhaustion During Chronic Viral Infection and Cancer

2019· review· en· 1,997 citations· W2912648593 on OpenAlex· 10.1146/annurev-immunol-041015-055318

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Abstract

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.

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The record

Venue
Annual Review of Immunology
Topic
Immune Cell Function and Interaction
Field
Immunology and Microbiology
Canadian institutions
Funders
Fonds de Recherche du Québec - SantéCanadian Institutes of Health ResearchParker Institute for Cancer ImmunotherapyCancer Research InstitutePublic Health AgencyNational Institutes of HealthPublic Health Agency of CanadaUniversity of Pennsylvania
Keywords
BiologyImmunologyEpigeneticsImmune checkpointImmune systemAutoimmunityCD8PopulationCancerCytotoxic T cellEffectorT cellChronic infectionBlockadeCancer researchImmunotherapyReceptorGeneticsMedicine
Has abstract in OpenAlex
yes