Tumor cells and tumor-associated stromal cells such as immune, endothelial and
mesenchimal cells create a Tumor Microenvironment (TME) which allows tumor cell promotion,
growth and dissemination while dampening the anti-tumor immune response. Efficient
anti-tumor interventions have to keep into consideration the complexity of the TME and take
advantage of immunotherapy and chemotherapy combined approaches. Thus, the aim of tumor
therapy is to directly hit tumor cells and reverse endothelial and immune cell anergy. Selective
targeting of tumor vasculature using TNFα-associated peptides or antibody fragments
in association with chemotherapeutic agents, has been shown to exert a potent stimulatory effect
on endothelial cells as well as on innate and adaptive immune responses. These drug
combinations reducing the dose of single agents employed have led to minimize the associated
side effects. In this review, we will analyze different TNFα-mediated tumor vesseltargeted
therapies in both humans and tumor mouse models, with emphasis on the role played
by the cross-talk between natural killer and dendritic cells and on the ability of TNFα to trigger
tumor vessel activation and normalization. The improvement of the TNFα-based therapy
with anti-angiogenic immunomodulatory drugs that may convert the TME from immunosuppressive
to immunostimulant, will be discussed as well.
Light-responsive CO2 bubble-generating polymeric micelles for tumor cell ablation
