CD27 is a costimulatory receptor of the TNF receptor superfamily expressed on T cells, B cells, and NK cells that binds its ligand CD70 to promote adaptive immune responses 1. The CD70-CD27 interaction mediates antigen-specific T-cell activation and expansion, providing immune surveillance of B cells 1. Mechanistically, CD70 ligation activates the TRAF2-PTPN6 axis, inhibiting LCK phosphorylation to promote T-cell memory formation 2. CD27 signaling requires both CD3 stimulation and functional Fc-receptor interaction for optimal T-cell activation 3. CD27+ γδ-T cells commit to IFN-γ production and play critical roles in anti-tumor immunity, with IL-27 supporting maturation of cytotoxic CD27+Ly6C+ subsets 4. In cancer, chr12 CD70-CD27 interaction paradoxically leads to T-cell exhaustion and dysfunction, with CD27 expression marking exhausted intratumoral T cells 5. Notably, soluble CD27 levels in patient plasma correlate with resistance to anti-PD-(L)1 immunotherapy, suggesting biomarker potential 5. Beyond T cells, CD27 identifies specific IL-10-producing regulatory B-cell subsets involved in maintaining immune homeostasis 6. CD27 agonist antibodies like MK-5890 show promise complementing checkpoint inhibition in cancer immunotherapy 3, though CD27 expression alone is insufficient to define human memory B cells 7.