Uric acid enhances the antitumor immunity of dendritic cell-based vaccine

Sci Rep. 2015 Nov 10:5:16427. doi: 10.1038/srep16427.

Abstract

Uric acid (UA) released from dying cells has been recognized by the immune system as a danger signal. In response to UA, dendritic cells (DC) in the immune system mature and enhance the T cell response to foreign antigens. It is conceivable that the antitumor immunity of a tumor vaccine could be promoted by the administration of UA. To test this concept, we applied UA as an adjuvant to a DC-based vaccine, and discovered that the administration of UA as an adjuvant significantly enhanced the ability of the tumor lysate-pulsed DC vaccine in delaying the tumor growth. The antitumor activity was achieved with adoptively transferred lymphocytes, and both CD8(+) T cells and NK cells were required to achieve effective immunity. This resulted in an increased accumulation of activated CD8(+) T cells and an elevated production of IFN-γ. Collectively, our study shows that the administration of UA enhances the antitumor activity of tumor lysate-pulsed DC vaccine, thus providing the preclinical rationale for the application of UA in DC-based vaccine strategies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic*
  • Adoptive Transfer
  • Animals
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / metabolism
  • Cancer Vaccines / immunology*
  • Cytokines / metabolism
  • Cytotoxicity, Immunologic
  • Dendritic Cells / immunology*
  • Disease Models, Animal
  • Female
  • Immunization
  • Immunoglobulins / administration & dosage
  • Interferon-gamma
  • Killer Cells, Natural / immunology
  • Killer Cells, Natural / metabolism
  • Lymphocyte Activation / immunology
  • Mice
  • Neoplasms / immunology*
  • Neoplasms / metabolism
  • Neoplasms / mortality
  • Neoplasms / therapy
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / metabolism
  • T-Lymphocytes, Cytotoxic / immunology
  • T-Lymphocytes, Cytotoxic / metabolism
  • Uric Acid* / administration & dosage
  • Uric Acid* / immunology
  • Uric Acid* / metabolism

Substances

  • Adjuvants, Immunologic
  • Cancer Vaccines
  • Cytokines
  • Immunoglobulins
  • Uric Acid
  • Interferon-gamma