TNFRSF8

TNFRSF8, also known as CD30, is a member of the tumor necrosis factor receptor (TNFR) superfamily. The gene TNFRSF8 is located on chromosome 1p36.22. CD30 encodes a type I transmembrane receptor involved in immune cell signaling.

CD30 is characterized by an extracellular domain with four cysteine-rich repeats and a cytoplasmic tail that engages adaptor proteins such as TRAF2 and TRAF5 to initiate downstream signaling. It is typically expressed on activated T cells, particularly Th2-skewed CD4+ T cells, and on subsets of B cells and natural killer cells. In pathology, CD30 is strongly expressed by classical Hodgkin lymphoma–associated Reed-Sternberg cells and by cells in anaplastic large cell lymphoma.

Its ligand, CD30 ligand (CD30L, TNFSF8), is expressed on activated T cells and B cells. Binding of CD30 and CD30L enables forward signaling in CD30-expressing cells and, in some contexts, bidirectional or reverse signaling that can influence T cell activation and cytokine production.

CD30 signaling activates NF-κB and MAPK pathways, promoting cell proliferation, survival, and cytokine secretion in some settings, while in others it can promote growth arrest or apoptosis, depending on cellular context and co-stimulatory signals.

Clinically, CD30 serves as an immunophenotypic marker and therapeutic target. Anti-CD30 therapies have transformed treatment for CD30-positive lymphomas. Brentuximab vedotin, an antibody-drug conjugate linking an anti-CD30 antibody to monomethyl auristatin E, is approved for relapsed or refractory classical Hodgkin lymphoma, systemic anaplastic large cell lymphoma, and CD30-positive cutaneous T-cell lymphomas.