INVESTIGATION OF THE IMMUNOSTIMULATORY EFFECT OF INTRACELLULAR PARASITES IN VIVO CANCER MODEL
Project no. 26 · Status: Kapanmış · 2016
Summary
Chemotherapy, radiation, and surgery are the very important classic tools in the cancer treatment. Although they can effectively kill or remove cancer cells, the use of these treatments often is restricted because big part of normal cells also tend to be damaged. Currently, there is a great deal of interest in developing treatments that stimulate effective immune responses against cancer in order to establish another major therapeutic option and improve outcomes. The immune system is effectively stimulated by microorganisms, which the possibility of using microorganisms as adjuvants to stimulate antitumor immunity has been recognized. The single cell eukaryotic parasite Leishmania spp preferentially invades macrophages. In vivo studies, this parasite generates a strong immune response, characterized by activation of antigen presenting cells to stimulate CD8+ T cell maturation and expansion with associated generation of high levels of IL-12 and IFN-?. Since such immune responses are associated with effective antitumor immunity, in study, we investigated whether Leishmania attenuated strains could induce the specific antitumor immunity required to eliminate tumor. As a result, we investigated Leishmania immunotherapy using a highly aggressive breast cancer model. We demonstrated that treatment of established 4T1 breast tumor by intratumoral injection of attenuated Leishmania strains regresses the primary tumor treatment. Also, this treatment increased expression of IFN and IL-12 production by Th1 and CD8+ T cells. The therapeutic benefit of Leishmania treatment relied on invasive parasites, IL-12 and IFN? production, and stimulated CD8+ T cells. Our findings demonstrated that immunotherapy with the attenuated Leishmania strains stimulated effective antitumor T-cell responses in solid tumors.