Programmed Death-Ligand 1 (PD-L1) is an immune checkpoint molecule expressed on antigen-presenting cells and various cancer cells, critically involved in modulating T-cell-mediated immune responses. Its interaction with programmed cell death protein 1 (PD-1) on activated T cells delivers inhibitory signals that suppress cytotoxic activity and promote immune tolerance-a mechanism exploited by malignancies to evade immune surveillance. Elevated PD-L1 expression has been documented across multiple tumor types including non-small cell lung carcinoma, melanoma, and gastrointestinal cancers, correlating with advanced disease progression and poorer prognostic outcomes.
CD27, a 50 kDa transmembrane glycoprotein belonging to the tumor necrosis factor receptor (TNFR) superfamily, exists as a disulfide-linked homodimer predominantly expressed on lymphocytes including mature T cells, memory B cells, NK cells, and thymocyte subsets. Its expression is tightly regulated by antigen receptor engagement, while its ligand CD70 requires co-stimulatory signals for induction. T-cell activation through TCR-CD3 complex enhances CD27 membrane expression and promotes shedding of soluble CD27 (sCD27), a 28-32 kDa proteolytic fragment detectable in biological fluids and serving as a prognostic biomarker in B-cell malignancies. CD27-CD70 interaction mediates bidirectional signaling critical for lymphocyte survival, differentiation, and immunological memory formation. However, this axis is counterregulated by proteolytic degradation via RgpA cysteine proteinase, which cleaves CD27 to inhibit T-cell activation. The CD27-SIVA interaction further modulates apoptotic signaling through TNFR-associated pathways.