Characterization of myeloid suppressor cells in an experimental model of metastatic renal adenocarcinoma

Abstract

The renal cell carcinoma (RCC) represents approximately 2 to 3% of human malignant tumors and is the most aggressive of urologic tumors. The most common is the subtype of RCC clear cell (ccRCC). Most patients have mutated gene tumor suppressor in von Hippel-Lindau (VHL) which results in increased transcription of several angiogenic factors such as vascular endothelial growth factor (VEGF). In addition to the angiogenic activity, VEGF can interfere negatively in adaptive tumor immune response. The tumor microenvironment contains a plurality of stromal cells such as T cells, B cells, natural killer (NK) cells, pericytes, fibroblasts, adipocytes and endothelial cells and myeloid suppressor cells (MSC), which coordinate collectively the course of the disease. The action of the MSC cells in the tumor microenvironment is one of the key factors of tumor evasion of the immune system, favoring tumor progression and metastasis. The endostatin (ES) is the product of cleavage of the carboxy-terminal portion of collagen XVIII. ES inhibits the proliferation, migration and stimulates apoptosis of endothelial cells and numerous studies have proven effective in the treatment of various tumor types. The treatment of primary and metastatic RCC in animal models resulted various changes in the tumor microenvironment such as reduction vessels and increased apoptosis and cellular necrosis, endothelial activation and increased inflammatory infiltrate. In this project, we intend to evaluate the impact of scenic therapy with ES in the modulation and expansion and suppressive activity of myeloid cells in the animal model of metastatic adenocarcinoma.