These data suggest that both CD8+T cells and NK cells may play important functions in the antitumor activity using the vaccination with TP-DC with 100g UA. == Physique 5. CD8+T cells and NK cells were required to accomplish effective immunity. This resulted in an increased accumulation of activated CD8+T cells and an elevated production of IFN-. 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. Malignant tumors have become a major problem in public health. Although standard chemotherapy remains the backbone of current treatment, it is still hindered by numerous side effects and developmental limitations1,2,3. Recent scientific advances have enhanced our understanding of the immune system and its role in attacking malignant cells. The tumor vaccine has evolved as an alternative treatment modality as it harnesses the bodys natural ability to identify and eliminate malignancy cells from the body. An effective tumor vaccine must possess the ability to induce a safe, antigen-specific and long-lasting immune response. In this regard, the use of dendritic cells (DC) in vaccine strategies has attracted a fair amount of attention. DC, derived from hematopoietic progenitor cells, are known as the sentinels of the immune system. They are the most powerful antigen presenting GSK591 cells with the ability to elicit both main and secondary immune responses to foreign antigens4,5. Immature DC firstly internalize and process antigens in peripheral tissues and then migrate to draining lymphoid organs, where they undergo maturation. Subsequently, they stimulate T cells through the up-regulation of cell-surface major histocompatibility complexes (MHC) and costimulatory molecules6,7. Immunization via DC loaded with tumor-associated antigens could potentially be a powerful strategy of inducing specific antitumor immunity. The usage of tumor lysates as a possible source of tumor-associated antigens is found to have several benefits, including mimicking the physiologic processes of tumor acknowledgement and rejection8. In present studies, several groups pulsed tumor lysates onto bone marrow-derived DC and used them for immunization in experimental animals. They have indicated that this tumor lysates-pulsed DC (TP-DC) vaccine is usually a powerful strategy of eliciting broader T cell immune responses8,9,10. However, this DC-based vaccine, although offering considerable advantages, still has a limited antitumor effect in GSK591 some cases, thus requiring the addition of adjuvants to elicit a strong and long-lasting immune response. The danger model has GSK591 proposed that antigen-presenting cells are activated by danger or alarm signals from hurt cells, thus promoting T cell responses to copresented antigens11. Recently, uric acid (UA) released from dying cells has been identified as a danger transmission for IRA1 the immune system12,13,14,15. UA is usually a natural product of the purine metabolic pathway and it is released from dying cells, which eventually prospects to crystallization. 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 antigens14,16. Crystalline UA has been shown to activate macrophages to produce inflammatory mediators11, and it may activate 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. Since we have been exploring approaches to enhance the protective and therapeutic activities of DC-based vaccines, we combined the administration of TP-DC and UA based on these existing studies. Collectively, our GSK591 results exhibited that UA enhanced the antitumor activity of TP-DC vaccine against tumors. == Results == == Induction of protective and therapeutic antitumor immunity == To investigate protective antitumor immunity, we immunized mice with TP-DC together with 100 g UA, TP-DC or saline on day 0, 14, 21 and challenged them with tumor cells at day 7 after the third immunization. Tumor growth inhibition was determined by the size of tumor. As shown inFig.1a, in E.G7 T lymphoma model, immunization using TP-DC with 100 g UA significantly inhibited the tumor growth compared to using TP-DC alone and the saline control groups. In addition, the percentage of tumor-free mice using TP-DC with 100 g UA and TP-DC alone was 40% and 30%, respectively, but the group immunized with saline experienced 100% tumor-bearing mice (Fig. 1b). Even though survival time was not significantly different between TP-DC and TP-DC with 100 g UA, they were both significantly longer than that of the.