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Cellular and molecular mechanisms of CD8+ T cell differentiation, dysfunction and exhaustion
journal contributionposted on 2020-11-17, 00:53 authored by DJ Verdon, M Mulazzani, Misty JenkinsMisty Jenkins
© 2020 by the authors. Licensee MDPI, Basel, Switzerland. T cells follow a triphasic distinct pathway of activation, proliferation and differentiation before becoming functionally and phenotypically “exhausted” in settings of chronic infection, autoimmunity and in cancer. Exhausted T cells progressively lose canonical effector functions, exhibit altered transcriptional networks and epigenetic signatures and gain constitutive expression of a broad coinhibitory receptor suite. This review outlines recent advances in our understanding of exhausted T cell biology and examines cellular and molecular mechanisms by which a state of dysfunction or exhaustion is established, and mechanisms by which exhausted T cells may still contribute to pathogen or tumour control. Further, this review describes our understanding of exhausted T cell heterogeneity and outlines the mechanisms by which checkpoint blockade differentially engages exhausted T cell subsets to overcome exhaustion and recover T cell function.
The authors would like to acknowledge the support of the Walter and Eliza Hall Institute of Medical Research. M.M. is funded by the German Cancer Aid (Mildred Scheel Postdoctoral Fellowship). M.R.J. is funded by NHMRC, The Walter and Eliza Hall Institute of Medical Research Suzanne Cory Fellowship, RCD Foundation and Cancer Australia
- School of Molecular Sciences