Our laboratory studies tumor immunobiology and designs immunotherapies for the treatment of cancer based results gained in translational murine models and human in vitro studies, with the near-term goal of developing novel phase I/II clinical trials for the treatment of patients with melanoma or renal cell carcinoma. Such modalities have included dendritic cell (DC)-based vaccines, cytokine gene-modified DC injected directly into tumor lesions and combinational approaches integrating agents that modulate tumor cell immune recognition or alter the balance or Type-1 versus regulatory immunity in the tumor microenvironment. Most recently, we have discovered that immune targeting of the tumor-associated vasculature occurs naturally as a consequence of effective immunotherapy (via DC1-based cross-priming of T cells), and that vaccines based on tumor-associated blood vessel antigens (TBVA) can promote tumor regression even in cases where cancer cells cannot be directly recognized by the protective CD8+ immune system. We have also recently determined that anti-angiogenic agents such as the TKIs sunitinib, axitinib and dasatinib all lead to tumor vascular normalization and to the improved delivery of anti-TBVA or anti-tumor T cells into the tumor microenvironment (TME) allowing for improve anti-tumor efficacy. Prospective interests include the therapeutic development of tertiary lymphoid structures (TLS) within the TME in vivo that effectively turn portions of the tumor into peripheral lymph node-like organs, where protective immunity may be initiated and better directed at proximal neoplastic cells and the trialing of combination immunotherapies integrating immune checkpoint inhibitors.