Koido Shigeo
Division of Gastroenterology and Hepatology, Department of Internal Medicine, The Jikei University School of Medicine, Kashiwa Hospital, 277-8567 Chiba, Japan.
Int J Mol Sci. 2016 May 26;17(6):828. doi: 10.3390/ijms17060828.
Dendritic cells (DCs) are potent antigen-presenting cells (APCs) that play a critical role in the induction of antitumor immunity. Therefore, various strategies have been developed to deliver tumor-associated antigens (TAAs) to DCs as cancer vaccines. The fusion of DCs and whole tumor cells to generate DC-tumor fusion cells (DC-tumor FCs) is an alternative strategy to treat cancer patients. The cell fusion method allows DCs to be exposed to the broad array of TAAs originally expressed by whole tumor cells. DCs then process TAAs endogenously and present them through major histocompatibility complex (MHC) class I and II pathways in the context of costimulatory molecules, resulting in simultaneous activation of both CD4⁺ and CD8⁺ T cells. DC-tumor FCs require optimized enhanced immunogenicity of both DCs and whole tumor cells. In this context, an effective fusion strategy also needs to produce immunogenic DC-tumor FCs. We discuss the potential ability of DC-tumor FCs and the recent progress in improving clinical outcomes by DC-tumor FC-based cancer vaccines.
树突状细胞(DCs)是强大的抗原呈递细胞(APCs),在诱导抗肿瘤免疫中起关键作用。因此,已经开发了各种策略将肿瘤相关抗原(TAAs)递送至DCs作为癌症疫苗。将DCs与整个肿瘤细胞融合以产生DC-肿瘤融合细胞(DC-肿瘤FCs)是治疗癌症患者的一种替代策略。细胞融合方法使DCs能够接触到整个肿瘤细胞最初表达的多种TAAs。然后,DCs在内源性地处理TAAs,并在共刺激分子的背景下通过主要组织相容性复合体(MHC)I类和II类途径呈递它们,从而导致CD4⁺和CD8⁺ T细胞同时被激活。DC-肿瘤FCs需要优化DCs和整个肿瘤细胞的增强免疫原性。在这种情况下,一种有效的融合策略还需要产生具有免疫原性的DC-肿瘤FCs。我们讨论了DC-肿瘤FCs的潜在能力以及基于DC-肿瘤FCs的癌症疫苗在改善临床结果方面的最新进展。