OPN (Osteopontin) is also referred to bone sialoprotein I (BSP-1 or BNSP), early T-lymphocyte activation (ETA-1), secreted phosphoprotein 1 (SPP1), 2ar and Rickettsia resistance (Ric). Human OPN protein molecule is encoded by the SPP1 gene (secreted phosphoprotein 1). Osteopontin is expressed by cells in a variety of tissues, including bone, dentin, cementum, hypertrophic cartilage, kidney, brain, bone-marrow-derived metrial gland cells, vascular tissues and cytotrophoblasts of the chorionic villus in the uterus and decidua, ganglia of the inner ear, brain cells and specialized epithelia found in mammary, salivary, and sweat glands, in bile and pancreatic ducts, and in distal renal tubules and in the gut, as well as in activated macrophages and lymphocytes.
4-1BB (also known as CD137 or TNFRSF9) is a type I transmembrane glycoprotein belonging to the tumor necrosis factor receptor superfamily (TNFRSF). It consists of 255 amino acids with a molecular weight of ~28 kDa, featuring an extracellular domain containing four cysteine-rich motifs, a transmembrane helix, and an intracellular domain critical for downstream signaling. Primarily expressed on activated T cells and natural killer (NK) cells, 4-1BB is upregulated upon T-cell receptor engagement and interacts with its ligand 4-1BBL, which is predominantly displayed on antigen-presenting cells (APCs) like dendritic cells and macrophages. This receptor-ligand interaction recruits TRAF adaptor proteins (TRAF1, TRAF2, TRAF3) to form signalosomes, activating NF-κB and MAPK pathways that enhance T-cell proliferation, cytotoxic activity, and pro-inflammatory cytokine production, while suppressing apoptosis through upregulated anti-apoptotic proteins like Bcl-2. As a pivotal co-stimulatory molecule in adaptive immunity, 4-1BB has emerged as a promising target for cancer immunotherapy.