Inhibition of dopamine receptor D3 signaling in dendritic cells increases antigen cross-presentation to CD8+ T-cells favoring anti-tumor immunity

J Neuroimmunol. 2017 Feb 15:303:99-107. doi: 10.1016/j.jneuroim.2016.12.014. Epub 2017 Jan 2.

Abstract

Dendritic cells (DCs) display the unique ability for cross-presenting antigens to CD8+ T-cells, promoting their differentiation into cytotoxic T-lymphocytes (CTLs), which play a pivotal role in anti-tumor immunity. Emerging evidence points to dopamine receptor D3 (D3R) as a key regulator of immunity. Accordingly, we studied how D3R regulates DCs function in anti-tumor immunity. The results show that D3R-deficiency in DCs enhanced expansion of CTLs in vivo and induced stronger anti-tumor immunity. Co-culture experiments indicated that D3R-inhibition in DCs potentiated antigen cross-presentation and CTLs activation. Our findings suggest that D3R in DCs constitutes a new therapeutic target to strengthen anti-tumor immunity.

Keywords: Antigen cross-presentation; Cytotoxic T lymphocytes; Dendritic cells; Dopamine receptors; Knockout mice; Tumor immunology.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigen Presentation / immunology
  • Antigens, Neoplasm / immunology*
  • Antigens, Neoplasm / metabolism
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / metabolism
  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism
  • Male
  • Melanoma, Experimental / immunology
  • Melanoma, Experimental / metabolism
  • Mice
  • Mice, 129 Strain
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Receptors, Dopamine D3 / deficiency*
  • Receptors, Dopamine D3 / immunology*
  • Signal Transduction / immunology
  • Tumor Burden / immunology*

Substances

  • Antigens, Neoplasm
  • Receptors, Dopamine D3