Furthermore, the anti-angiogenic activity of platycodin D was

confirmed by performing the Matrigel plug assay in mice. In a mouse tumor xenograft model, platycodin D inhibited the growth of MDA-MB-231 breast carcinoma, and reduced the expression of VEGF, CD34 and IL-8. Taken together, our results indicate that platycodin TH-302 solubility dmso D exerts anti-angiogenic action by regulating MAPKs activation and IL-8 expression. Therefore, platycodin D may beneficial for prevention and treatment of angiogenesis-dependent human diseases such as tumor. Poster No. 85 Role of Complement in Lymphoid-Like Tumor Transformation and Invasion Iraklis C. Kourtis 1 , Jacqueline D. Shields1, Melody A. Swartz1 1 Institute of Bioengineering, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Vaud, Switzerland Changes in the immunological equilibrium in the tumor microenvironment are critical for the progression of a developing tumor, allowing tumor escape from immune surveillance and metastases. We have identified that invasive B16 F10 melanomas

naturally secrete CCL21, a ligand for CCR7, which is used by dendritic cells and naïve T cells to home to the T cell zone of the lymph node to initiate an immune response. B16 F10 melanoma cells were engineered to either knockdown, maintain or over-express CCL21. Chemokine secreting tumors, but not knockdown variants, attracted CCR7+ lymphoid tissue inducer cells (LTis, CD45+CD3−CD4+IL-7Ra+ROR-γt+) into the tumor and drove lymphoid-like changes in the tumor Selleckchem Buparlisib microenvironment including a reticular fibroblast stromal network (CCL21+gp38+ ERTR7+LYVE-1−) surrounding the tumor, HEV-like vessels (ERTR7+ PNAds+LYVE-1−) inside the tumor, and, importantly, an overexpression of complement regulating receptors. This microenvironment, reminiscent of the T cell zone in the lymph node, attracted naive T cells into the tumor where, we hypothesized, they could be educated towards a tolerogenic phenotype only in a regulatory

microenvironment. Recent studies have suggested a role of complement in tumor growth, and since complement can serve both immune regulatory and functional roles depending its processed form, we implanted clonidine these tumors into C3-/- mice. We found that both CCL21 expressing and knockdown tumors grew poorly, and CCL21-secreting tumors could not drive a regulatory T cell response as they did in wild type mice. These findings suggest that invasive tumors may utilize complement dependent strategies in the newly formed quasi lymph node microenvironment, to further provide a regulatory environment for in situ education of T cells shifting the host immune response from a functional to regulatory repertoire. Poster No.