Baylor Institute for Immunology Research, 3434 Live Oak, Dallas, TX 75204, USA.
Curr Top Microbiol Immunol. 2011;344:173-92. doi: 10.1007/82_2010_48.
Current active immunotherapy trials have shown durable tumor regressions in a fraction of patients. However, the clinical efficacy of current vaccines is limited, possibly because tumors skew the immune system by means of myeloid-derived suppressor cells, inflammatory Type 2 T cells and regulatory T cells (Tregs), all of which prevent the generation of effector cells. To improve the clinical efficacy of cancer vaccines in patients with metastatic disease, we need to design novel and improved strategies that can boost adaptive immunity to cancer, help overcome Tregs and allow the breakdown of the immunosuppressive tumor microenvironment. This can be achieved by exploiting the fast increasing knowledge about the dendritic cell (DC) system, including the existence of distinct DC subsets. Critical to the design of better vaccines is the concept of distinct DC subsets and distinct DC activation pathways, all contributing to the generation of unique adaptive immune responses. Such novel DC vaccines will be used as monotherapy in patients with resected disease and in combination with antibodies and/or drugs targeting suppressor pathways and modulation of the tumor environment in patients with metastatic disease.
目前的主动免疫疗法试验已经在一部分患者中显示出了持久的肿瘤消退。然而，目前疫苗的临床疗效有限，这可能是因为肿瘤通过髓系来源的抑制细胞、炎症性 2 型 T 细胞和调节性 T 细胞（Tregs）来扭曲免疫系统，所有这些都会阻止效应细胞的产生。为了提高转移性疾病患者癌症疫苗的临床疗效，我们需要设计新的、改进的策略，以增强对癌症的适应性免疫，帮助克服 Tregs 并允许抑制性肿瘤微环境的崩溃。这可以通过利用关于树突状细胞（DC）系统的快速增长的知识来实现，包括不同的 DC 亚群的存在。设计更好的疫苗的关键是不同的 DC 亚群和不同的 DC 激活途径的概念，所有这些都有助于产生独特的适应性免疫反应。这种新型的 DC 疫苗将作为单一疗法用于切除疾病的患者，并与针对抑制途径的抗体和/或药物以及转移性疾病患者肿瘤环境的调节联合使用。
