Ramos Rodrigo Nalio, de Moraes Cristiano Jacob, Zelante Bruna, Barbuto José Alexandre M
Department of Immunology, Institute of Biomedical Sciences, University of Sao Paulo, Avenida Professor Lineu Prestes, 1730 Sao Paulo, SP, Brazil.
Clin Dev Immunol. 2013;2013:806025. doi: 10.1155/2013/806025. Epub 2013 May 22.
Dendritic cells (DCs) are essential for the maintenance of homeostasis in the organism, and they do that by modulating lymphocyte priming, expansion, and response patterns according to signals they receive from the environment. The induction of suppressive lymphocytes by DCs is essential to hinder the development of autoimmune diseases but can be reverted against homeostasis when in the context of neoplasia. In this setting, the induction of suppressive or regulatory T cells contributes to the establishment of a state of tolerance towards the tumor, allowing it to grow unchecked by an otherwise functional immune system. Besides affecting its local environment, tumor also has been described as potent sources of anti-inflammatory/suppressive factors, which may act systemically, generating defects in the differentiation and maturation of immune cells, far beyond the immediate vicinity of the tumor mass. Cytokines, as IL-10 and TGF-beta, as well as cell surface molecules like PD-L1 and ICOS seem to be significantly involved in the redirection of DCs towards tolerance induction, and recent data suggest that tumor cells may, indeed, modulate distinct DCs subpopulations through the involvement of these molecules. It is to be expected that the identification of such molecules should provide molecular targets for more effective immunotherapeutic approaches to cancer.
树突状细胞（DCs）对于维持机体的内环境稳态至关重要，它们通过根据从环境中接收到的信号来调节淋巴细胞的启动、扩增和反应模式来实现这一点。DCs诱导抑制性淋巴细胞对于阻碍自身免疫性疾病的发展至关重要，但在肿瘤形成的情况下，这可能会破坏内环境稳态。在这种情况下，诱导抑制性或调节性T细胞有助于建立对肿瘤的耐受状态，使肿瘤能够在原本功能正常的免疫系统下不受控制地生长。除了影响其局部环境外，肿瘤还被描述为抗炎/抑制因子的强大来源，这些因子可能会在全身发挥作用，导致免疫细胞的分化和成熟出现缺陷，远远超出肿瘤块的直接周边区域。细胞因子，如白细胞介素-10（IL-10）和转化生长因子-β（TGF-β），以及细胞表面分子如程序性死亡配体1（PD-L1）和诱导共刺激分子（ICOS）似乎在DCs向诱导耐受方向的重编程中发挥着重要作用，最近的数据表明肿瘤细胞确实可能通过这些分子的参与来调节不同的DCs亚群。可以预期，识别这些分子应该为更有效的癌症免疫治疗方法提供分子靶点。
