Uric acid promotes tumor immune rejection

Cancer Res. 2004 Aug 1;64(15):5059-62. doi: 10.1158/0008-5472.CAN-04-1586.

Abstract

Uric acid released from dying cells has been shown recently to act as a danger signal for the immune system, stimulating dendritic cell maturation and enhancing T-cell responses to foreign antigens. Stimulation of dendritic cell maturation by uric acid has been proposed as a mechanism by which the immune system could generate responses against tumors. We show here that uric acid levels are elevated in tumors undergoing immune rejection and that the inhibition of uric acid production, by systemic administration of allopurinol, or the removal of uric acid, by administration of uricase, delayed tumor immune rejection, whereas subcutaneous administration of crystalline uric acid enhanced the rejection process.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Allopurinol / pharmacology
  • Animals
  • Apoptosis / drug effects
  • Apoptosis / immunology
  • Cell Division / drug effects
  • Cell Division / immunology
  • Chickens
  • Enzyme Inhibitors / pharmacology
  • Female
  • Graft Rejection / etiology*
  • Graft Rejection / metabolism
  • Immune System / drug effects
  • Injections, Subcutaneous
  • Mice
  • Mice, Inbred C57BL
  • Neoplasm Transplantation / immunology
  • Ovalbumin / genetics
  • Ovalbumin / metabolism
  • Thymoma / immunology*
  • Thymoma / pathology
  • Thymus Neoplasms / immunology*
  • Thymus Neoplasms / metabolism
  • Thymus Neoplasms / pathology
  • Urate Oxidase / metabolism
  • Uric Acid / metabolism
  • Uric Acid / pharmacology*

Substances

  • Enzyme Inhibitors
  • Uric Acid
  • Allopurinol
  • Ovalbumin
  • Urate Oxidase