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0This research article investigates how the orphan nuclear receptor Nur77 serves as a vital transcriptional regulator that boosts Natural Killer (NK) cell immunity against hepatocellular carcinoma (HCC). By utilizing spatial and single-cell transcriptomics, the authors demonstrate that Nur77 expression correlates with improved patient survival and enhanced NK cell activation through AP-1 gene networks. The study reveals that a deficiency in this receptor impairs NK cell maturation and allows for faster tumor growth, whereas Nur77 agonism using the small molecule Cytosporone B restores anti-tumor functions. Mechanistically, activating Nur77 suppresses the metabolic checkpoint CD36, which protects NK cells from lipid-mediated immunosuppression within the hostile tumor environment. Ultimately, the findings suggest that pre-treating NK cells with Nur77 agonists could significantly enhance the effectiveness of adoptive immunotherapy for solid tumors.
References:
Neo S Y, Mei Y, Chong J, et al. Nur77 agonism invigorates Natural Killer cell immunity against hepatocellular carcinoma[J]. Nature Communications, 2026.
