Abstract A19: Characterizing the tumor stroma of B16 melanoma at different sites

The stromal cells of the tumor microenvironment play a critical role in tumor progression, and are therefore attractive targets for cancer therapy. We previously used the stromal targeting agent, 5,6-dimethylxanthenone-4-acetic acid (DMXAA), to demonstrate how tumor and stromal interactions can be manipulated to favor anti-tumor activity against human melanoma xenografts in immunodeficient mice, mediated by neutrophils and macrophages. An ideal stromal targeting agent would be effective against established metastases as well as primary tumors. In order to design such therapies, and to assess their potential, a better understanding of the tumor microenvironment at the various sites is required. The aim of this study was to characterize the tumor stroma of established B16-F10 murine melanoma tumors at subcutaneous, pulmonary, and intracranial sites, in syngeneic C57BL/6 mice. Immunofluorescence-immunohistochemistry and flow cytometry were used to identify infiltrating leukocyte populations within B16-F10 tumors at these different sites. Furthermore, the antitumor activity of DMXAA against this model was investigated. In subcutaneous tumors, monocytic myeloid cells (CD11b+ F4/80-/dim) and macrophages (CD11b+ F4/80+) were found predominantly around the tumor periphery. Lymphocyte infiltration was variable, with B-cells (CD19+ B220+) and T-cells (CD3+ CD4+ and CD3+ CD8+) rarely detected in some tumors, but scattered diffusely or formed dense lymphoid structures throughout necrotic...
Source: Cancer Research - Category: Cancer & Oncology Authors: Tags: Innate Immune Cells in the Tumor Microenvironment Source Type: research