Mitochondrial stress induced by continuous stimulation under hypoxia rapidly drives T cell exhaustion

Cancer and chronic infections induce T cell exhaustion, a hypofunctional fate carrying distinct epigenetic, transcriptomic and metabolic characteristics. However, drivers of exhaustion remain poorly understood. As intratumoral exhausted T cells experience severe hypoxia, we hypothesized that metabol...

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Veröffentlicht in:	Nature immunology 2021-02, Vol.22 (2), p.205-215
Hauptverfasser:	Scharping, Nicole E., Rivadeneira, Dayana B., Menk, Ashley V., Vignali, Paolo D. A., Ford, B. Rhodes, Rittenhouse, Natalie L., Peralta, Ronal, Wang, Yiyang, Wang, Yupeng, DePeaux, Kristin, Poholek, Amanda C., Delgoffe, Greg M.
Format:	Artikel
Sprache:	eng
Schlagworte:	631/250/1619/554/1834/1269 631/250/2152/569/2495 631/250/2502 631/250/580 Animals Biomedical and Life Sciences Biomedicine CD8 antigen CD8-Positive T-Lymphocytes - immunology CD8-Positive T-Lymphocytes - metabolism Cell differentiation Cell Line, Tumor Cell metabolism Coculture Techniques Energy Metabolism Epigenetics Female Health aspects HEK293 Cells Humans Hypoxia Immunological research Immunology Immunotherapy Infectious Diseases Lymphocyte Activation Lymphocytes Lymphocytes, Tumor-Infiltrating - immunology Lymphocytes, Tumor-Infiltrating - metabolism Male Melanoma, Experimental - genetics Melanoma, Experimental - immunology Melanoma, Experimental - metabolism Melanoma, Experimental - pathology Metabolism Mice Mice, Inbred C57BL Mice, Transgenic Mitochondria Mitochondria - immunology Mitochondria - metabolism NF-AT protein Oxidative stress Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha - genetics Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha - metabolism Physiological aspects Positive Regulatory Domain I-Binding Factor 1 - genetics Positive Regulatory Domain I-Binding Factor 1 - metabolism Reactive oxygen species Reactive Oxygen Species - metabolism Signal Transduction T cell receptors T cells Transcription factors Tumor Hypoxia Tumor Microenvironment
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