Hanke Neale, Alizadeh Darya, Katsanis Emmanuel, Larmonier Nicolas
Department of Pediatrics, Steele Children's Research Center, University of Arizona, Tucson, Arizona 85724-5073, USA.
Crit Rev Immunol. 2013;33(1):1-21. doi: 10.1615/critrevimmunol.2013006679.
Universally viewed as the sentinels and messengers of the immune system and traditionally referred to as professional antigen-presenting cells, dendritic cells (DCs) play a fundamental role in antitumor immunity. DCs are uniquely equipped with the ability to acquire, process, and present to T lymphocytes tumor-derived antigens. They can drive the differentiation of naive T cells into activated tumor-specific effector lymphocytes. DCs also dictate the type and regulate the strength and duration of T-cell responses. In addition, they contribute to natural killer and natural killer T-cell antitumoral function and to B-cell-mediated immunity. Besides this cardinal role as orchestrators of innate and adaptive immune responses, many studies have provided evidence that DCs can also function as direct cytotoxic effectors against tumors. This less conventional aspect of DC function has, however, raised controversy as it relates to the origin of these cells and the induction, regulation, and mechanisms underlying their tumoricidal activity. The possible impact of the cytotoxic function of DCs on their capability to present antigens also has been the focus of intensive research. This review examines these questions and discusses the biological significance of this nontraditional property and possible strategies to exploit the killing potential of DCs in cancer immunotherapy.
树突状细胞(DCs)被普遍视为免疫系统的哨兵和信使,传统上被称为专职抗原呈递细胞,在抗肿瘤免疫中发挥着重要作用。DCs具有独特的能力,能够获取、处理并向T淋巴细胞呈递肿瘤衍生抗原。它们可以促使幼稚T细胞分化为活化的肿瘤特异性效应淋巴细胞。DCs还决定T细胞反应的类型,并调节其强度和持续时间。此外,它们有助于自然杀伤细胞和自然杀伤T细胞的抗肿瘤功能以及B细胞介导的免疫。除了作为先天性和适应性免疫反应的协调者这一主要作用外,许多研究已提供证据表明,DCs还可作为针对肿瘤的直接细胞毒性效应器发挥作用。然而,DC功能的这一不太传统的方面引发了争议,因为它涉及这些细胞的起源以及其杀肿瘤活性的诱导、调节和机制。DCs的细胞毒性功能对其呈递抗原能力的可能影响也一直是深入研究的焦点。本综述探讨了这些问题,并讨论了这种非传统特性的生物学意义以及在癌症免疫治疗中利用DCs杀伤潜力的可能策略。