TNFR2 Human

TNFR2 is a member of the tumor necrosis factor receptor superfamily . The extracellular region of TNFR2 consists of four cysteine-rich domains that facilitate binding to TNFα . Unlike its counterpart, Tumor Necrosis Factor Receptor 1 (TNFR1), TNFR2 lacks a death domain (DD), which means it does not directly induce apoptosis .

When TNFα binds to TNFR2, it leads to the recruitment of anti-apoptotic proteins such as c-IAP1 and c-IAP2, which possess E3 ubiquitin ligase activity . These proteins are thought to potentiate TNF-induced apoptosis by ubiquitinating and degrading TNF-receptor-associated factor 2 (TRAF2), which mediates anti-apoptotic signals .

TNFR2 plays a significant role in various physiological and pathological processes. It is neuroprotective, partly because it lacks an intracellular death domain . Increased levels of soluble TNFR2 (sTNFR2) have been observed in patients with schizophrenia .

In the context of cancer, TNFR2 is associated with increased tumor cell death and decreased progression of tumor cell growth . Increased expression of TNFR2 has been found in several types of cancer, including breast, cervical, colon, and renal cancers . Targeting TNFR2 in tumor cells has shown potential for therapeutic applications, as it can lead to increased tumor cell death and inhibition of tumor growth .

Recent research has highlighted the potential of TNFR2 as a therapeutic target in cancer therapy . TNFR2 promotes tumor immune escape by stimulating various immune suppressive cell types, such as regulatory T-cells (Tregs) and myeloid-derived suppressor cells (MDSCs) . However, TNFR2 also elicits antitumoral activities by costimulating cytotoxic T-cells .

Both antagonists and agonists targeting TNFR2 have been preclinically evaluated for tumor therapy and have demonstrated anti-tumor activity in preclinical studies . The dual role of TNFR2 in promoting immune suppression and stimulating cytotoxic T-cells makes it a complex but promising target for cancer treatment .