Shurin Michael R, Shurin Galina V, Lokshin Anna, Yurkovetsky Zoya R, Gutkin Dmitry W, Chatta Gurkamal, Zhong Hua, Han Baohui, Ferris Robert L
Department of Pathology, University of Pittsburgh Medical Center and Cancer Institute, Pittsburgh, PA 15213, USA.
Cancer Metastasis Rev. 2006 Sep;25(3):333-56. doi: 10.1007/s10555-006-9010-6.
The tumor microenvironment consists of a variable combination of tumor cells, stromal fibroblasts, endothelial cells and infiltrating leukocytes, such as macrophages, T lymphocytes, and dendritic cells. A variety of cytokines, chemokines and growth factors are produced in the local tumor environment by different cells accounting for a complex cell interaction and regulation of differentiation, activation, function and survival of multiple cell types. The interaction between cytokines, chemokines, growth factors and their receptors forms a comprehensive network at the tumor site, which is primary responsible for overall tumor progression and spreading or induction of antitumor immune responses and tumor rejection. Although the general thought is that dendritic cells are among the first cells migrating to the tumor site and recognizing tumor cells for the induction of specific antitumor immunity, the clinical relevance of dendritic cells at the site of the tumor remains a matter of debate regarding their role in the generation of successful antitumor immune responses in human cancers. While several lines of evidence suggest that intratumoral dendritic cells play an important role in antitumor immune responses, understanding the mechanisms of dendritic cell/tumor cell interaction and modulation of activity and function of different dendritic cell subtypes at the tumor site is incomplete. This review is limited to discussing the role of intratumoral cytokine network in the understanding immunobiology of tumor-associated dendritic cells, which seems to possess different regulatory functions at the tumor site.
肿瘤微环境由肿瘤细胞、基质成纤维细胞、内皮细胞和浸润性白细胞（如巨噬细胞、T淋巴细胞和树突状细胞）的可变组合构成。不同细胞在局部肿瘤环境中产生多种细胞因子、趋化因子和生长因子，这构成了复杂的细胞间相互作用，并对多种细胞类型的分化、激活、功能和存活进行调节。细胞因子、趋化因子、生长因子及其受体之间的相互作用在肿瘤部位形成了一个综合网络，该网络主要负责肿瘤的整体进展、扩散或诱导抗肿瘤免疫反应及肿瘤排斥。尽管一般认为树突状细胞是最早迁移至肿瘤部位并识别肿瘤细胞以诱导特异性抗肿瘤免疫的细胞之一，但肿瘤部位树突状细胞在人类癌症成功抗肿瘤免疫反应生成中的作用在临床相关性方面仍存在争议。虽然有几条证据表明肿瘤内树突状细胞在抗肿瘤免疫反应中起重要作用，但对肿瘤部位树突状细胞/肿瘤细胞相互作用机制以及不同树突状细胞亚群活性和功能调节的理解仍不完整。本综述限于讨论肿瘤内细胞因子网络在理解肿瘤相关树突状细胞免疫生物学中的作用，肿瘤相关树突状细胞在肿瘤部位似乎具有不同的调节功能。
