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

Yuquan Wei,Chao Su,Hongyuan Jia,Bin Peng,Chunju Fang,Min Luo,Jing Du,Yihan Wang,Xuelei Ma

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.

Highlights

(UA) released from dying cells has been identified as a danger signal for the immune system[12,13,14,15]
The percentage of tumor-free mice using TP-dendritic cells (DC) with 100 μ g UA and TP-DC alone was 40% and 30%, respectively, but the group immunized with saline had 100% tumor-bearing mice (Fig. 1b)
DC are professional antigen presenting cells playing a vital role in the initiation, programming and regulation of tumor-specific immune responses[17,18]

Summary

Introduction

(UA) released from dying cells has been identified as a danger signal for the immune system[12,13,14,15]. It was reported that crystalline UA stimulates the maturation of DC by increasing the expression of costimulatory molecules CD80 and CD86, and enhances T cell responses to foreign antigens[14,16]. Crystalline UA has been shown to activate macrophages to produce inflammatory mediators[11], and it may stimulate DC in a similar way. It is conceivable that UA, an endogenous danger signal, could be used as a potential adjuvant to DC-based vaccines for potent antitumor immunity. Our results demonstrated that UA enhanced the antitumor activity of TP-DC vaccine against tumors

Methods

Results

Conclusion