LIGHT/TNFSF14 (E1Y2S) Rabbit mAb #53373

Tumor necrosis factor superfamily member 14 (TNFSF14), also known as CD258 and LIGHT, is a cell surface type II transmembrane protein that is expressed as a homotrimer (1). The extracellular region can be cleaved to generate a soluble cytokine (2). TNFSF14 is a ligand for the receptors herpesvirus entry mediator (HVEM) and lymphotoxin receptor (LTR) (1). TNFSF14 is expressed on activated NK cells, activated T cells, activated monocytes, immature DCs, and mast cells (1,3,4). TNFSF14 interactions with HVEM induce potent co-stimulatory signaling in T cells and trigger NK cells to produce IFN-γ via NF-κB RelA/p50 pathway signaling (5,6). TNFRSF14 produced by tumor-sensing NK cells aids in DC maturation, enabling de novo anti-tumor adaptive immune responses (7). TNFSF14-HVEM interactions are considered the main drivers of anti-tumor immune responses, whereas TNFSF14-LTR interactions have been characterized as maintaining the infrastructure that supports the anti-tumor response via lymphoid development and cancer cells’ susceptibility to the immune response (8,9). TNFSF14 induces the normalization of tumor vasculature, sensitizes tumor cells to IFN-γ-mediated apoptosis, and results in a more inflamed tumor microenvironment (TME) (6,8,10,11). Due to its effects on the TME and anti-tumor immune cell responses, TNFSF14 is being investigated as a target for immunotherapeutic intervention in cancer (9). TNFSF14 has also been implicated in the development and pathogenesis of inflammatory bowel disease and airway remodeling leading to asthma (12,13).