Research ArticleImmunology

Tumor-derived TGF-β inhibits mitochondrial respiration to suppress IFN-γ production by human CD4+ T cells

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Science Signaling  17 Sep 2019:
Vol. 12, Issue 599, eaav3334
DOI: 10.1126/scisignal.aav3334

Suppressing antitumor immunity

The cytokine TGF-β has both immune-suppressive and tumor-suppressive functions; thus, a better understanding of the cell-type specificity of the effects of TGF-β might improve therapeutic strategies that target it. Dimeloe et al. found that TGF-β from tumor effusions suppressed the antitumor activity of CD4+ T cells by inhibiting their production of the inflammatory cytokine IFN-γ. The effects of TGF-β were mediated by Smad proteins in the mitochondria, rather than in the nucleus, and led to decreased mitochondrial respiration. Indeed, direct inhibition of a mitochondrial electron transport chain complex in CD4+ T cells was sufficient to inhibit IFN-γ production. Thus, these data suggest that TGF-β targets T cell metabolism to suppress antitumor immunity.

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