文章：

通过树突状细胞进行癌症免疫治疗

Cancer immunotherapy via dendritic cells

原文发布日期：2012-03-22

DOI: 10.1038/nrc3258

类型: Review Article

开放获取: 否

要点：

1. The molecular identification of human cancer antigens has allowed the development of antigen-specific immunotherapy. In one approach, autologous antigen-specific T cells are expanded ex vivo and then re-infused into patients. Another approach is through vaccination; that is, the provision of an antigen together with an adjuvant to elicit therapeutic T cells in vivo. Cancer vaccines aim to induce tumour-specific effector T cells that can reduce the tumour mass and to induce tumour-specific memory T cells that can control tumour relapse.
2. Owing to their properties, dendritic cells (DCs) are often called 'nature's adjuvants' and thus have become the natural targets for antigen delivery. DCs provide an essential link between the innate and the adaptive immune responses. DCs are at the centre of the immune system owing to their ability to control both tolerance and immune responses. These key properties of DCs render them the central candidates for antigen delivery and vaccination, including therapeutic vaccination against cancer.
3. The immune system has the potential to eliminate neoplastic cells. However, tumour cells alone are poor antigen-presenting cells (APCs). Studies with mouse models demonstrate that the generation of protective anti-tumour immune responses depends on the presentation of tumour antigens by DCs. When compared with other APCs, such as macrophages, DCs are extremely efficient at antigen presentation and inducing T cell immunity, thus explaining their nickname of 'professional APCs'.
4. Mice and humans have distinct functional subsets of DCs that generate different types of immune response. DCs are also able to mature; that is, to acquire novel functions following microbe encounters. Under steady state conditions, DCs in peripheral tissues are 'immature'. These immature DCs induce tolerance either through T cell deletion or through inducing the expansion of regulatory and/or suppressor T cells. DCs promptly respond to environmental signals and differentiate into mature DCs that can efficiently launch immune responses. It is now accepted that the adjuvant component of vaccines primarily acts by triggering DC maturation.
5. DCs are important targets for therapeutic interventions in cancer. Two themes of research are growing: first, how cancer cells alter DC physiology; and second, how we can build on the powerful properties of DCs to generate novel cancer immunotherapies (including vaccines).

要点翻译：

1. 人类癌症抗原的分子鉴定使得抗原特异性免疫疗法得以发展。一种方法是自体抗原特异性T细胞在体外扩增后回输患者体内。另一种方法是通过疫苗接种，即提供抗原与佐剂联合在体内诱导治疗性T细胞。癌症疫苗旨在诱导能够减少肿瘤负荷的肿瘤特异性效应T细胞，以及能够控制肿瘤复发的肿瘤特异性记忆T细胞。
2. 基于其特性，树突状细胞常被称为"天然佐剂"，因此成为抗原递送的自然靶标。树突状细胞在先天性和适应性免疫应答之间建立了关键连接。由于其同时调控免疫耐受与免疫应答的能力，树突状细胞处于免疫系统的核心位置。这些关键特性使树突状细胞成为抗原递送和疫苗接种（包括癌症治疗性疫苗）的核心候选载体。
3. 免疫系统具有清除肿瘤细胞的潜力。然而肿瘤细胞本身是低效的抗原呈递细胞。小鼠模型研究表明，保护性抗肿瘤免疫应答的生成依赖于树突状细胞对肿瘤抗原的呈递。与巨噬细胞等其他抗原呈递细胞相比，树突状细胞在抗原呈递和诱导T细胞免疫方面具有极高效率，因此被誉为"专职抗原呈递细胞"。
4. 小鼠和人类拥有不同的树突状细胞功能亚群，可激发不同类型的免疫应答。树突状细胞还具有成熟能力，即在接触微生物后获得新功能。在稳态条件下，外周组织中的树突状细胞处于"未成熟"状态，这些未成熟树突状细胞通过T细胞清除或诱导调节性/抑制性T细胞扩增来建立免疫耐受。树突状细胞能迅速响应环境信号，分化为能有效启动免疫应答的成熟树突状细胞。目前公认疫苗中的佐剂成分主要通过触发树突状细胞成熟发挥作用。
5. 树突状细胞是癌症治疗干预的重要靶标。两大研究主题日益突出：一是癌细胞如何改变树突状细胞生理功能；二是如何基于树突状细胞的强大特性开发新型癌症免疫疗法（包括疫苗）。

英文摘要：

Cancer immunotherapy attempts to harness the power and specificity of the immune system to treat tumours. The molecular identification of human cancer-specific antigens has allowed the development of antigen-specific immunotherapy. In one approach, autologous antigen-specific T cells are expanded ex vivo and then re-infused into patients. Another approach is through vaccination; that is, the provision of an antigen together with an adjuvant to elicit therapeutic T cells in vivo. Owing to their properties, dendritic cells (DCs) are often called 'nature's adjuvants' and thus have become the natural agents for antigen delivery. After four decades of research, it is now clear that DCs are at the centre of the immune system owing to their ability to control both immune tolerance and immunity. Thus, DCs are an essential target in efforts to generate therapeutic immunity against cancer.

摘要翻译： 

癌症免疫疗法试图利用免疫系统的力量和特异性来治疗肿瘤。人类癌症特异性抗原的分子鉴定使得抗原特异性免疫疗法的发展成为可能。一种方法是，将自体抗原特异性T细胞在体外扩增后重新输注到患者体内。另一种方法是疫苗接种；即提供抗原与佐剂共同在体内诱导治疗性T细胞。由于其特性，树突状细胞（DC）常被称为“自然佐剂”，因此成为抗原递送的自然载体。经过四十年的研究，现已明确，DC因其调控免疫耐受与免疫应答的能力而处于免疫系统的核心地位。因此，DC是产生抗癌治疗性免疫应答的关键靶点。

原文链接：

Cancer immunotherapy via dendritic cells