Tumor necrosis factor receptor superfamily member 1A and 1B (TNFR1/TNFR2)

Tumor necrosis factor receptor 1 (TNFR1) and Tumor necrosis factor receptor 2 (TNFR2) are transmembrane receptors that mediate the biological effects of the cytokine TNF-alpha (UniProt P19438, P20333). In the context of cisplatin chemotherapy, these receptors are critical mediators of cisplatin-induced nephrotoxicity, a major dose-limiting side effect (Ramesh & Reeves, 2002, J Clin Invest). Cisplatin exposure induces the expression and release of TNF-alpha, which subsequently activates TNFR1 and TNFR2, triggering pro-inflammatory and pro-apoptotic signaling pathways in renal tubular cells (PubMed PMID: 17431114). TNFR1 contains a death domain that directly initiates apoptosis, while TNFR2 contributes to the inflammatory milieu and can also influence cell survival. Therapeutic strategies targeting these receptors or their ligand, TNF-alpha, have been investigated to mitigate kidney injury during platinum-based treatment (NIH). Understanding the interplay between cisplatin and the TNFR signaling axis is essential for improving the safety profile of chemotherapy in cancer patients.

Other names

Tumor necrosis factor receptor 1Tumor necrosis factor receptor 2TNFRSF1ATNFRSF1BCD120aCD120bTNF-R1TNF-R2p55p75

Cisplatin induces the production and release of TNF-alpha, which activates TNFR1 and TNFR2 to trigger pro-inflammatory and pro-apoptotic signaling pathways in renal tubular cells; therapeutic TNF inhibitors neutralize the ligand to prevent this receptor-mediated toxicity.