TNFRSF9 (4-1BB) is a tumor necrosis factor receptor family member that functions as a costimulatory receptor for CD8+ T cells. Upon engagement by its ligand TNFSF9 (4-1BBL), it enhances T-cell survival, cytotoxicity, and mitochondrial activity, promoting anti-viral and anti-tumor immunity. Early work demonstrated that antibody-mediated ligation of TNFRSF9 augmented T-cell proliferation in vitro 1, and that the receptor is preferentially expressed on activated T cells and can be detected on tumor-infiltrating lymphocytes 2. In cancer immunotherapy, TNFRSF9 has emerged as a key costimulatory domain in engineered T-cell therapies: chimeric antigen receptors (CARs) incorporating 4-1BB costimulation have been approved for B-cell lymphomas and acute lymphoblastic leukemia, with efficacy comparable to CD28-costimulated alternatives 3. Recent clinical development has advanced bispecific antibodies targeting both TNFRSF9 and PD-L1 (such as ABL503), which synergize with anti-PD1 checkpoint inhibitors to reinvigorate exhausted tumor-infiltrating CD8+ T cells and enhance anti-tumor responses in hepatocellular carcinoma and ovarian cancer 4. Additionally, TNFRSF9 is a susceptibility gene for EBV-associated immunodeficiency in primary immune regulatory disorders.