Immune adjuvant effect of a Toxoplasma gondii profilin-like protein in autologous whole-tumor-cell vaccination in mice

Oncotarget. 2016 Nov 8;7(45):74107-74119. 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.

Keywords: Toll-like receptor; Toxoplasma gondii; antitumor; profilin; vaccine.

MeSH terms

  • Adjuvants, Immunologic / pharmacology*
  • Animals
  • Cancer Vaccines / immunology
  • Cancer Vaccines / pharmacology*
  • Cell Line, Tumor
  • Colonic Neoplasms / immunology
  • Colonic Neoplasms / therapy
  • Female
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Profilins / immunology
  • Profilins / pharmacology*
  • Signal Transduction
  • Toxoplasma / immunology*

Substances

  • Adjuvants, Immunologic
  • Cancer Vaccines
  • Profilins