Redlinger Richard E, Mailliard Robbie B, Barksdale Edward M
Department of Surgery, University of Pittsburgh School of Medicine, Division of Pediatric Surgery, Children's Hospital of Pittsburgh, Pittsburgh, PA 15213-2583, USA.
Semin Pediatr Surg. 2004 Feb;13(1):61-71. doi: 10.1053/j.sempedsurg.2003.09.009.
Neuroblastoma, the most common extracranial solid tumor of childhood, remains a challenge for clinicians and investigators in pediatric surgical oncology. The absence of effective conventional therapies for most patients with neuroblastoma justifies the application of novel, biology-based, experimental approaches to the treatment of this deadly disease. The observation that some aggressive neuroblastomas, particularly in infants, may spontaneously regress suggested that immune-mediated mechanisms may be important in the biology of this disease. Advances in the understanding of the cognate interactions between T cells, antigen-presenting cells and tumors have demonstrated the sentinel role of dendritic cells (DC), the most potent antigen presenting cells, in initiating the cellular immune response to cancer. Until recently the function of DC in pediatric solid tumors, especially neuroblastoma, had not been extensively studied. This review discusses the role of DC in initiating and coordinating the immune response against cancer, the ability of neuroblastoma to induce DC dysregulation at multiple levels by inhibiting DC maturation and function, and the current vaccine strategies being designed to employ the unique ability of DC to promote neuroblastoma regression.
神经母细胞瘤是儿童最常见的颅外实体瘤,对于小儿外科肿瘤学的临床医生和研究人员而言,它仍然是一个挑战。由于大多数神经母细胞瘤患者缺乏有效的传统治疗方法,因此应用基于生物学的新型实验性方法来治疗这种致命疾病是合理的。一些侵袭性神经母细胞瘤,尤其是婴儿患者的神经母细胞瘤可能会自发消退,这一观察结果表明免疫介导机制在该疾病的生物学过程中可能很重要。对T细胞、抗原呈递细胞和肿瘤之间同源相互作用的认识进展表明,树突状细胞(DC)作为最强大的抗原呈递细胞,在启动针对癌症的细胞免疫反应中发挥着哨兵作用。直到最近,DC在小儿实体瘤,尤其是神经母细胞瘤中的功能尚未得到广泛研究。本文综述了DC在启动和协调抗癌免疫反应中的作用、神经母细胞瘤通过抑制DC成熟和功能在多个水平诱导DC失调的能力,以及目前旨在利用DC促进神经母细胞瘤消退的独特能力而设计的疫苗策略。