Tumor necrosis factor receptor 1 (TNFR1) and Tumor necrosis factor receptor 2 (TNFR2) (TNFR1/TNFR2)

Tumor necrosis factor receptor 1 (TNFR1) and Tumor necrosis factor receptor 2 (TNFR2) are the primary cell surface receptors for the cytokine tumor necrosis factor-alpha (TNF-alpha) [1, 2]. TNFR1 is ubiquitously expressed and contains an intracellular death domain that can trigger either pro-inflammatory signaling via NF-κB or programmed cell death through apoptosis and necroptosis [1, 3]. In contrast, TNFR2 is primarily expressed on immune cells and endothelial cells, lacks a death domain, and generally promotes cell survival, tissue repair, and immune regulation [2, 3]. Dysregulation of the TNF/TNFR signaling axis is a hallmark of various chronic inflammatory and autoimmune conditions, including rheumatoid arthritis, psoriasis, and inflammatory bowel disease [3, 5]. Therapeutic strategies have historically focused on neutralizing the TNF-alpha ligand using monoclonal antibodies or decoy receptors like etanercept, which effectively block signaling through both receptors [4, 5]. Emerging research is focused on selective targeting, such as TNFR1 antagonists to reduce inflammation while sparing TNFR2-mediated tissue protection, or TNFR2 agonists to enhance regulatory T-cell function in autoimmune diseases [3]. These receptors also play complex roles in cancer, where TNFR1 can induce tumor cell death while TNFR2 may promote an immunosuppressive tumor microenvironment [3]. Safety concerns for drugs targeting this pathway include an increased risk of serious infections and potential malignancy [4, 5].

Other names

TNFRSF1ATNFRSF1BCD120aCD120bp55p75TNF-R1TNF-R2Tumor necrosis factor receptor superfamily member 1ATumor necrosis factor receptor superfamily member 1B

Neutralization of TNF-alpha ligand to prevent receptor activation; selective antagonism of TNFR1; selective agonism or antagonism of TNFR2 [3, 4, 5].