{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nTMIGD2—also known as CD28H or IGPR-1—is emerging as a key immune checkpoint receptor with dual roles in both immune modulation and cancer biology. In immune cells, TMIGD2 is constitutively expressed on naive T lymphocytes and natural killer (NK) cells, where it mediates costimulatory signals upon binding its ligand, HHLA2. This interaction has been shown to promote T‐cell proliferation and cytokine production via AKT‐dependent signaling, and its expression pattern has been linked to varying prognostic implications in several cancers, including pancreatic ductal adenocarcinoma, oral squamous cell carcinoma, gastric cancer, hepatocellular carcinoma, and glioma. TMIGD2 thereby contributes to the fine balance between immune activation and tolerance, with its expression correlating with improved antitumor responses in certain contexts yet also associating with immune escape in others."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "8"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its immunomodulatory functions, TMIGD2 (IGPR-1) plays an important role in endothelial biology. It localizes at endothelial cell–cell contacts and, through homophilic interactions, regulates adhesion, cellular morphology, and mechanosensing. Activation of TMIGD2 promotes the assembly of actin stress fibers and the stabilization of adherens junctions, thereby enhancing barrier function and modulating angiogenesis. Furthermore, TMIGD2 has been implicated in autophagy regulation in endothelial cells, linking its adhesive and mechanotransductive capacities to broader homeostatic processes such as capillary tube formation and cellular stress responses."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "9", "end_ref": "13"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Yuwen Zhu, Sheng Yao, Bettina P Iliopoulou, et al. 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