The promise of 4-1BB (CD137) mediated immunomodulation and immunotherapy for viral diseases

The T-cell surface receptor, 4-1BB (CD137), has been of increasing interest to immunologists as a co-stimulatory immune checkpoint molecule over the last two decades. Ligation of 4-1BB can activate signals in CD8⁺ T cells and NK cells, resulting in increased proinflammatory cytokine secretion, cytolytic function and antibody-dependent cell-mediated cytotoxicity. Targeting 4-1BB, using a 4-1BB ligand (4-1BBL) or agonistic monoclonal antibodies, has delivered a new strategy to fight against cancer, autoimmune diseases and viral infections. In this review, different aspects of 4-1BB mediated antiviral responses, the mechanistic basis of such responses and future directions are discussed.