TNFRSF7/CD27

TNFRSF7/CD27 is a TNF receptor family costimulatory receptor whose CD70-dependent signaling supports T- and B-cell activation^[1][2]. Mechanistically, CD27 engagement provides a second signal for T-cell activation and can activate NF-κB and JNK through TRAF-associated signaling^[3][4]. In naïve CD8⁺ T cells, CD27-CD70 interaction promotes memory-associated gene regulatory networks through a CD27-TRAF2-SHP-1 axis^[5]. In experimental immunity models, CD27 is required for generation and long-term maintenance of T-cell immunity^[6]. Human CD27 deficiency links TNFRSF7 loss to persistent symptomatic EBV viremia, impaired T-cell-dependent antibody generation, severe EBV infection, Hodgkin lymphoma, and primary antibody deficiency^[7][8]. Compared with membrane-bound CD27, soluble CD27 is released after TCR/CD3 triggering and is elevated in serum from cancer patients after immunotherapy, making isoform distinction important for biomarker interpretation^[9]. For experimental applications, varlilumab is an agonist anti-CD27 antibody evaluated in advanced solid tumors and in combination with nivolumab, providing a practical tool to study CD27 pathway activation in cancer immunology^[10][11].