The TNF receptor superfamily member herpesvirus entry mediator (HVEM or TNFRSF14), first identified as a receptor for viral infection, acts as a molecular switch, either activating or inhibiting the immune response depending on the interacting ligand. Previous work found that HVEM binding to B- and T-lymphocyte attenuator (BTLA) initiates an inhibitory signal to effector T cells and that targeting the HVEM-BTLA complex with an antibody reduced tumor growth in a humanized mouse model.