Tumor necrosis factor receptor superfamily member 14 (TNFRSF14) (HVEM)

Tumor necrosis factor receptor superfamily member 14 (TNFRSF14), commonly known as Herpesvirus entry mediator (HVEM), is a versatile type I transmembrane protein that serves as a critical immune checkpoint and molecular switch on T cells [1, 3]. It is unique among the TNF receptor superfamily for its ability to engage in bidirectional signaling with multiple ligands from different protein families, including the TNF-related ligand LIGHT and the immunoglobulin superfamily members BTLA and CD160 [4, 13]. Interaction with LIGHT typically provides co-stimulatory signals that enhance T cell proliferation and survival, whereas binding to BTLA or CD160 delivers inhibitory signals that dampen immune responses [3, 11]. In the context of oncology, many tumors exploit the HVEM-BTLA axis to evade immune surveillance, and mutations in the TNFRSF14 gene are frequently observed in lymphomas, where they contribute to disease progression [7, 9]. Therapeutic strategies targeting this pathway include monoclonal antibodies and bispecific molecules designed to block inhibitory interactions or promote stimulatory signaling to restore anti-tumor immunity [4, 14]. Additionally, HVEM is a well-known entry receptor for Herpes simplex virus (HSV), facilitating viral infection of host cells [1, 12]. Recent research also highlights its role in T cell metabolic reprogramming via the HVEM-GPT2 axis, suggesting broader implications for cellular energetics in the tumor microenvironment [10].

Other names

Herpesvirus entry mediatorCD270LIGHTRTR2ATARHVEATNFRSF14

Modulation of the HVEM-BTLA/CD160 inhibitory axis or the HVEM-LIGHT stimulatory axis to regulate T cell-mediated immune responses.