TNFRSF4 and neoplasm: While DC-tumor hybrids alone are insufficient to elicit significant immune responses in vivo and are critically dependent upon exogenously administered 3rd signal adjuvants, murine studies using DC-tumor hybrids for vaccination given concomitantly with an adjuvant third signal, such as IL-12, OX-40-, 4-1BB-monoclonal antibody, or toll-like receptor agonists, showed regression of tumor metastases after a single vaccination in several tumor types including melanoma, breast, sarcoma, and squamous cell carcinoma [8–11].