Title: Immune adjuvant effect of a<i>Toxoplasma gondii</i>profilin-like protein in autologous whole-tumor-cell vaccination in mice
Abstract: // Kyoung-Ho Pyo 1, 4 , You-Won Lee 1 , Sun Min Lim 2 , Eun-Hee Shin 1, 3 1 Department of Parasitology and Tropical Medicine, Seoul National University College of Medicine and Institute of Endemic Diseases, Seoul National University Medical Research Center, Seoul, Republic of Korea 2 Division of Medical Oncology, Department of Internal Medicine, CHA Bundang Medical Center, CHA University, Republic of Korea 3 Seoul National University Bundang Hospital, Seongnam, Republic of Korea 4 Current address: JE-UK Laboratory of Molecular Cancer Therapeutics, Yonsei Cancer Institute, Yonsei University College of Medicine, Seoul, Republic of Korea Correspondence to: Eun-Hee Shin, email: [email protected] Keywords: Toxoplasma gondii, Toll-like receptor, profilin, antitumor, vaccine Received: July 15, 2016 Accepted: September 21, 2016 Published: September 28, 2016 ABSTRACT Profilin-like protein in Toxoplasma gondii (TgPLP) is a Toll-like receptor (TLR) agonist. In this study, we investigated whether TgPLP has an adjuvant effect on immune function in autologous whole-tumor-cell vaccine (AWV) treatment. Mice vaccinated with AWV together with recombinant TgPLP protein had smaller CT26 tumors and increased survival. TgPLP treatment strongly increased the production of IL-12 through MyD88 signaling and several chemokines, including CCL5, CCL12, and XCL1, in bone marrow-derived macrophages (BMMs). In addition, TgPLP increased the phagocytosis of tumor cells by BMMs and promoted immune cell mobility on a tumor-matrigel scaffold. TgPLP triggered immune responses as demonstrated by increased expression of antigen presenting cell markers (MHC class I and II, B7.1, and B7.2) in BMMs and increased IL-12 and IFN-γ expression in mice. Mice vaccinated with AWV and TgPLP had more immune cells (CD4 + and CD8 + T cells, natural killer cells, and macrophages) in the spleen and higher total IgG and IgG2a concentrations in the blood than mice vaccinated with AWV alone. These findings suggest that TgPLP is a TLR-based vaccine adjuvant that enhances antitumor immune responses during vaccination with AWV.