期刊
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
卷 21, 期 19, 页码 -出版社
MDPI
DOI: 10.3390/ijms21197357
关键词
T cell exhaustion; chronic viral infections; cancer; immunotherapy; epigenetics; PD-1; inhibitory receptors
资金
- Walter and Eliza Hall Institute of Medical Research
- German Cancer Aid (Mildred Scheel Postdoctoral Fellowship)
- NHMRC
- The Walter and Eliza Hall Institute of Medical Research Suzanne Cory Fellowship
- RCD Foundation
- Cancer Australia
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.
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