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Beyond Cell Death: New Functions for TNF Family Cytokines in Autoimmunity and Tumor Immunotherapy.

ABSTRACT: Originally discovered as an inducer of apoptosis, the TNF-family receptor Fas (CD95, APO-1, TNFRSF6) has more recently been found to have functions beyond cell death, including T cell co-stimulation and promoting terminal differentiation of CD4+ and CD8+ T cells. Other TNF family members also discovered as apoptosis inducers, such as TRAIL (APO-2L, TNFSF10), can promote inflammation through caspase-8. Surprisingly, non-apoptotic signaling through Fas can protect from the autoimmunity seen in Fas deficiency independently from the cell death inducing functions of the receptor. Non-apoptotic Fas signaling can induce tumor cell growth and migration, and impair the efficacy of T cell adoptive immunotherapy. Blocking of non-apoptotic functions of these receptors may be a novel strategy to regulate autoimmunity and inflammation, and enhance antitumor immunity.

SUBMITTER: Yi F

PROVIDER: S-EPMC7466867 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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Beyond Cell Death: New Functions for TNF Family Cytokines in Autoimmunity and Tumor Immunotherapy.

Yi Fei F Frazzette Nicholas N Cruz Anthony C AC Klebanoff Christopher A CA Siegel Richard M RM

Trends in molecular medicine 20180604 7

Originally discovered as an inducer of apoptosis, the TNF-family receptor Fas (CD95, APO-1, TNFRSF6) has more recently been found to have functions beyond cell death, including T cell co-stimulation and promoting terminal differentiation of CD4<sup>+</sup> and CD8<sup>+</sup> T cells. Other TNF family members also discovered as apoptosis inducers, such as TRAIL (APO-2L, TNFSF10), can promote inflammation through caspase-8. Surprisingly, non-apoptotic signaling through Fas can protect from the au ...[more]

PMID: 29880309

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