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.
ICOS (CD278), a member of the CD28 superfamily of costimulatory molecules, is a type I transmembrane glycoprotein expressed predominantly on activated T lymphocytes. Structurally, it comprises an extracellular immunoglobulin (Ig)-like variable (V) domain and a constant (C) domain forming a characteristic Ig-fold tertiary structure, followed by a transmembrane helix and a cytoplasmic tail containing conserved tyrosine-based signaling motifs. This configuration facilitates ligand binding through its extracellular V domain and initiates intracellular signaling via phosphoinositide 3-kinase (PI3K) recruitment upon engagement with ICOS ligand (ICOS-L) on antigen-presenting cells. Functionally, CD278 mediates critical costimulatory signals for T-cell activation and differentiation, particularly in follicular helper T (Tfh) cells and regulatory T (Treg) cells. Its interaction with ICOS-L potentiates IL-4, IL-10, and IL-21 production, driving germinal center formation and antibody class-switching.