CD27 receptor–CD70 ligand signaling pathway (CD27–CD70 pathway)

The CD70/CD27 signaling pathway mediates immune cell activation and survival through costimulatory interactions primarily between the CD27 receptor on lymphocytes (T, B cells, and NK cells) and the CD70 ligand on activated immune and tumor cells. Under normal physiological conditions, the pathway regulates lymphocyte proliferation, survival, memory formation, and immune tolerance. In cancers and chronic immune dysregulation, aberrant expression of CD70 and/or CD27 drives tumor growth by promoting stemness, local immunosuppression (via expansion of regulatory T cells and TAMs), and resistance to immune attack. Therapeutic strategies targeting this pathway are in advanced pre-clinical and clinical stages, particularly for leukemias and solid tumors that overexpress CD70, using monoclonal antibodies, immune checkpoint blockade, and combination immunotherapy. Soluble CD27 in patient serum serves as a biomarker for disease activity and poor prognosis in malignancies like AML. The pathway’s modulation presents both therapeutic opportunity and risk of unwanted broad immune suppression.

Other names

Tumor necrosis factor receptor superfamily 7 (CD27, TNFRSF7)Tumor necrosis factor ligand superfamily 7 (CD70, TNFSF7)CD27LLPFS3CD27-LCD27LGTNLG8A

Blocking CD70/CD27 signaling inhibits immunosuppressive Treg expansion, restores anti-tumor immune activity, reduces tumor cell stemness, promotes differentiation, and limits malignant cell proliferation. Some agonists may stimulate cytotoxic T-cell generation for immunotherapy.