Polarization of Tumor Milieu: Therapeutic Implications

摘要: During neoplastic progression, cancer cells recruit inflammatory (monocytes, neutrophils, mast, and dendritic cells, etc.), which become “educated” under the influence of factors released by (mainly cytokines). As a consequence, former lose their ability to present antigens. Instead, they involved in remodeling extracellular matrix stimulate formation blood vessels (angiogenesis). Proangiogenic act as immunosuppressants tumor milieu becomes proangiogenic immunosuppressive. Latest studies have demonstrated possibility reverting such proangiogenic/immunosuppressive microenvironment inhibits growth. Reverted anti-angiogenic immunostimulatory. Reversal is especially feasible with combinations immunomodulatory factors. For instance, VEGF, VEGFR2, or TGF-β activity inhibitors immunostimulants anticancer vaccines, CpG sequences, IL-12 were effective inhibiting growth experimental tumors. In our hands, DNA vaccine directed against endoglin (CD105), vascular endothelial cell-surface protein, when combined IL-12, led ca. 30 % cure rate mice bearing melanoma It appears that attempts therapeutically revert might merit further consideration.