Abstract

Dendritic cells (DCs) are a population of professional antigen presenting cells (APCs), serving as central regulators of adaptive immunity by presenting antigens. In addition, DCs play essential roles in the connection of the innate and adaptive immune responses. Recently, therapeutic vaccines turn out to become a viable therapeutic approach for immunotherapy of cancers. Here we report a dendritic cell-based vaccine strategy which could suppress the bladder tumor growth in vivo and improve the efficiency of chemotherapy. In this study, we investigate the antitumor effects of mature DCs induced by antigen loading in bladder tumor in vivo. We demonstrate the co-culture of cisplatin induced apoptotic human bladder cancer cell line, T24 cells with immature DCs could promote the maturation of DCs. Cisplatin and these activated DCs were reintroduced into mice bearing the T24 cisplatin resistant cells-derived tumor growth to activate or boost the immune response. Mice with iDCs co-cultured with apoptotic T24 (iDCs T24 Apo) cells injection effectively initiate a cytotoxic effect against tumor growth and improve the survival rates of mice compared with controls. Moreover, we observed injection of iDCs T24 apoptosis cells combined with cisplatin into mice with T24 cisplatin resistant cancer cells-derived tumor resulted in a statistically significant suppression of tumor growth compared with mice injected with PBS alone, cisplatin alone, iDCs, iDCs T24 Apo cells, cisplatin plus iDCs. This study provides a dendritic cell-based vaccine strategy which might reduce the risk of tumor recurrence and improve the efficiency of anti-chemoresistance of bladder cancer.

Highlights

  • Dendritic cells (DCs) form a population of professional antigen presenting cells (APCs), which control immune responses through innate and adaptive immunity [1]

  • It has been known that the tumor vaccine generated through antigen loading from apoptotic cancer cells could stimulate strong immune response since the tumor antigens originate from abnormally expressed endogenous proteins are derived from viral proteins

  • Recent studies demonstrated that apoptotic liver cancer cells and colorectal carcinoma cells have the abilities to stimulate the maturation of DCs [20, 21]

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Summary

Introduction

Dendritic cells (DCs) form a population of professional antigen presenting cells (APCs), which control immune responses through innate and adaptive immunity [1]. It is known that DCs could uptake, process and present multiple types of antigens to antigen-specific naïve T cells [3, 4]. Immature DCs express relatively low levels of surface MHC-I and MHC-II and costimulatory molecules such as CD80 and CD86 [6, 7]. Immature DCs display a specialized function as antigen-capturing cells. They are unable to process and present antigens efficiently to T cells [8]. Mature DCs express cell surface molecules important for T cell activation [9]. Activation and maturation of DCs with different maturation stimuli is associated with the local microenvironment and can be blocked or polarized by specific factors [10]

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