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Michael R Shurin

Michael R Shurin

University of Pittsburgh, USA

Title: Pharmacological regulation of the tumor immunoenvironment

Biography

After graduation from Moscow State Medical School in 1984, Post graduation training in clinical Biochemistry and Clinical Immunology and obtaining his PhD degree in Immunopharmacology in 1991, He joined the Faculty of the Department of Pathology at the University of Pittsburgh Medical Center in 1991 where he is a Professor of Pathology and Immunology and an Associate Director of the Division of Clinical Immunopathology. His main research interests are in the field of the tumour microenvironment, cancer-mediated immunomodulation and dendritic cell vaccines for cancer immunotherapy. At present, his research program focuses on the immune modulating properties of chemotherapy and modulation of the tumour micro environmental elements, including dendritic cells, regulatory T cells, myeloid-derived suppressor cells and endothelial cells, as well as intratumoral cytokine network. Using a combination of immunological, molecular and gene therapeutic methodologies, He is an Author of more than hundred peer-reviewed publications and numerous reviews, an editor of several books, including “Dendritic Cell in Cancer” and “The tumour immune environment” books, an organizer of several popular international conferences on Immune-Mediated Diseases, Immunodiagnostics and Immuno monitoring and Cancer Immunotherapy. He is a Member of several grant review and editorial boards and many clinical and research societies.

Abstract

The tumour microenvironment consist of a variable combination of tumour cells, stromal fibroblasts, endothelial cells and infiltrating leukocytes, such as macrophages, T lymphocytes, and Dendritic Cells (DC). Tumour progression is often associated with suppression or malfunction of the immune system, including the appearance of regulatory T cells and myeloid-derived suppressor cells, dysbalance of dendritic cell subsets and cytokine network, and polarization of Th1/Th2/Th3/Th17/Treg subsets and their balance. We have recently reported that antineoplastic chemotherapeutic agents could directly up-regulate development and functional activation of dendritic cells in vitro and in vivo if used in low nontoxic concentrations. Our new data revealed that low-dose nontoxic chemotherapy (or chemomodulation) increases resistance of dendritic cells to tumor-induced immunosuppression and converts suppressor dendritic cells into immunostimulatory cells. Furthermore, low-dose nontoxic chemotherapy down-regulated activity of myeloid-derived suppressor cells and regulatory T cells in the tumor microenvironment. Finally, antineoplastic chemotherapeutic agents in low, nontoxic concentrations blocked the ability of tumor cells to inhibit immune cell function. This effect was associated with increased expression of antigen-processing machinery components in tumor cells and, thus, increased immunogenicity of tumor cells. Together, these data suggest that the modulation of the tumor microenvironment by low-dose nontoxic chemotherapy – chemomodulation, - may serve as a powerful adjuvant for different immunotherapeutic modalities in cancer. In fact, application of low-dose chemotherapy prior to dendritic cell vaccines in the animal tumor models resulted in significant inhibition of primary and metastatic tumor growth in vivo. Thus, chemomodulation of the tumor environment with nontoxic doses of several common chemotherapeutic agents, including nanovehicle delivery of these agents, might target different cell populations, decrease tumor-induced immunosuppression, and improve the efficacy of modern vaccines for cancer therapy.