Ficolin-2 triggers antitumor effect by activating macrophages and CD8+ T cells

Clin Immunol. 2017 Oct:183:145-157. doi: 10.1016/j.clim.2017.08.012. Epub 2017 Aug 26.

Abstract

Ficolin-2 is an important serum complement lectin. Here, we describe novel findings indicating that serum ficolin-2 concentrations in multiple tumor patients are significantly lower than those in healthy donors. Administration of exogenous ficolin-2 or ficolin-A (a ficolin-2-like molecule in mouse), with only once, could remarkably inhibit the tumor cells growth in murine tumor models via early macrophages, dendritic cells (DCs) and CD8+ T cells, but not CD4+ T cells. Ficolin-A (FCN-A) knockout (KO) mice exhibits significantly increased tumor cell growth. Ficolin-2 induces macrophage activation, promotes M1 polarization and facilitates proliferation and antigen-specific cytotoxicity of CD8+ T cells. Ficolin-2 binds to Toll-like receptor 4 (TLR4) on macrophages and DCs and promotes their antigen-presenting abilities to CD8+ T cells. Our findings provide a new therapeutic strategy for tumors based on the triggering of immune-mediated antitumor effect by ficolin-2.

Keywords: Antitumor effect; CD8(+) T; Dendritic cells (DCs); Ficolin-2/A; Macrophage.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Animals
  • Breast Neoplasms / blood
  • CD8-Positive T-Lymphocytes / immunology*
  • Carcinoma, Hepatocellular / blood
  • Carcinoma, Lewis Lung
  • Cell Line, Tumor
  • Cell Proliferation*
  • Chemokine CCL5 / immunology
  • Colorectal Neoplasms / blood
  • Dendritic Cells / immunology
  • Female
  • Ficolins
  • Humans
  • Interleukin-6 / immunology
  • Lectins / blood
  • Lectins / genetics
  • Lectins / immunology*
  • Liver Neoplasms / blood
  • Lung Neoplasms / blood
  • Macrophage Activation / immunology*
  • Macrophages / immunology*
  • Male
  • Mice
  • Mice, Knockout
  • Middle Aged
  • Neoplasms / blood*
  • Nitric Oxide / immunology
  • Toll-Like Receptor 4 / immunology
  • Tumor Necrosis Factor-alpha / immunology

Substances

  • Ccl5 protein, mouse
  • Chemokine CCL5
  • Interleukin-6
  • Lectins
  • Tlr4 protein, mouse
  • Toll-Like Receptor 4
  • Tumor Necrosis Factor-alpha
  • interleukin-6, mouse
  • Nitric Oxide