Uric acid promotes tumor immune rejection.
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.
Hu
De-En
DE
Department of Biochemistry, University of Cambridge, 80 Tennis Court Road, Cambridge CB2 1GA, United Kingdom.
Moore
Alistair M
AM
Thomsen
Lindy L
LL
Brindle
Kevin M
KM
D000493:Allopurinol / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology; D002455:Cell Division / Q000187:drug effects / Q000276:immunology; D002645:Chickens; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006084:Graft Rejection / Q000209:etiology* / Q000378:metabolism; D007107:Immune System / Q000187:drug effects; D007279:Injections, Subcutaneous; D051379:Mice; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation / Q000276:immunology; D010047:Ovalbumin / Q000235:genetics / Q000378:metabolism; D013945:Thymoma / Q000276:immunology* / Q000473:pathology; D013953:Thymus Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D014503:Urate Oxidase / Q000378:metabolism; D014527:Uric Acid / Q000378:metabolism / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D014527:Uric Acid; D000493:Allopurinol; D010047:Ovalbumin; D014503:Urate Oxidase