{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n BTN3A3 is a member of the butyrophilin 3 family that, although highly homologous in its extracellular region to BTN3A1, displays distinct functional properties in immunity and cancer. In studies of phosphoantigen‐mediated activation of Vγ9Vδ2 T cells, a gain‐of‐function mutation in the intracellular B30.2 domain of the otherwise nonstimulatory BTN3A3 was shown to confer the ability to bind phosphoantigens and trigger T‐cell activation, highlighting the importance of intracellular sensing for this T‐cell population."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In the context of cancer, BTN3A3 has emerged as a receptor on breast cancer cells for LSECtin—an interaction that promotes cancer stemness, with in vivo studies demonstrating that disruption of the LSECtin–BTN3A3 axis can reduce cancer growth."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": " Genetic analyses have further implicated BTN3A3 in disease; specific BTN3A3 variants associate with differential viral genotype selection in hepatitis C infection"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": ", while downregulation of BTN3A3 in non‐small cell lung cancer correlates with advanced clinical stage, increased cell proliferation and poorer overall survival."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " In hepatocellular carcinoma and breast cancer, BTN3A3 expression is part of prognostic risk models, indicating its potential utility as a biomarker for tumor progression and patient outcome."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " Furthermore, transcriptional studies have identified BTN3A3 as one of several genes whose expression is modulated by the interplay between BLIMP1 and interferon regulatory factors, suggesting that BTN3A3 is integrated into immune‐regulatory networks that balance activation and suppression."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": " Finally, BTN3A3 polymorphisms have also been linked to altered risk of ovarian cancer, and its inclusion among interferon‐inducible genes hints at a broader role in antiviral responses."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Andrew Sandstrom, Cassie-Marie Peigné, Alexandra Léger, et al. 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