Immune adjuvant effect of aToxoplasma gondiiprofilin-like protein in autologous whole-tumor-cell vaccination in mice

Kyoung-Ho Pyo,You-Won Lee,Sun Min Lim,Eun-Hee Shin

doi:10.18632/oncotarget.12316

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.

Highlights

Autologous whole-tumor-cell vaccines (AWVs) are an established treatment for preventing tumor recurrence [1]
These findings suggest that TgPLP is a Toll-like receptor (TLR)-based vaccine adjuvant that enhances antitumor immune responses during vaccination with AWV
Vaccine adjuvants trigger an early innate immune response against tumor-associated antigens (TAAs), which is essential for promoting further adaptive immunity to cancer, such as the activation of cytotoxic CD8+ T cells

Summary

Introduction

Autologous whole-tumor-cell vaccines (AWVs) are an established treatment for preventing tumor recurrence [1]. Toll-like receptors (TLRs) induce IL-12 production via MyD88 signaling and improve vaccine efficacy by enhancing innate immunity and antigen presentation to activate T cells and adaptive immunity [9]. Conditional disruption of the TgPLP gene in T. gondii prevented gliding mobility and TLR 11-dependent IL-12 production by host immune cells [11]. This suggested that TgPLP is an essential component of gliding mobility as like bacterial flagellin and a microbial ligand recognized by the host immune system, both of which are important for T. gondii infection [11]

Methods

Results

Conclusion