Combined Tumor Cell-Based Vaccination and Interleukin-12 Gene Therapy Polarizes the Tumor Microenvironment in XXXX .

@entity20770 @entity5 @entity19 @entity1961 @entity320
UNASSIGNED: Tumor progression depends on @entity5 milieu, which influences neovasculature formation and immunosuppression. Combining immunotherapy with antiangiogenic/antivascular therapy might be an effective therapeutic approach. The aim of our study was to elaborate an anticancer therapeutic strategy based on the induction of immune response which leads to polarization of @entity5 milieu. To achieve this, we developed a @entity5 cell-based vaccine. @entity20770 peptide was used as a B16-F10 cell death-inducing agent. The lysates were used as a vaccine to immunize @entity19 bearing B16-F10 @entity320 . To further improve the therapeutic effect of the vaccine, we combined it with interleukin (IL)-12 gene therapy. IL-12, a cytokine with antiangiogenic properties, activates nonspecific and specific immune responses. We observed that combined therapy is significantly more effective (as compared with monotherapies) in inhibiting @entity5 growth. Furthermore, the tested combination polarizes the @entity5 microenvironment, which results in a switch from a proangiogenic/immunosuppressive to an antiangiogenic/immunostimulatory one. The switch manifests itself as a decreased number of @entity5 blood vessels, increased levels of @entity5 -infiltrating @entity1961 (+), CD8(+) and NK cells, as well as lower level of suppressor lymphocytes (Treg). Our results suggest that polarizing @entity5 milieu by such combined therapy does inhibit @entity5 growth and seems to be a promising therapeutic strategy.
