Takeuchi Hiroya, Kitajima Masaki, Kitagawa Yuko
Department of Surgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
Cancer Sci. 2008 Mar;99(3):441-50. doi: 10.1111/j.1349-7006.2007.00672.x. Epub 2007 Dec 7.
The sentinel lymph node (SLN) is defined as the lymph node(s) first receiving lymphatic drainage from the site of the primary tumor. The histopathological status of SLN is one of the most significant predictors of recurrence and overall survival for most clinical stage I/II solid tumors. Recent progress in molecular techniques has demonstrated the presence of micrometastatic tumor cells in SLN. There is now a growing body of data to support the clinical relevance of SLN micrometastasis in a variety of solid tumors. Increasing the sensitivity of occult tumor cell detection in the SLN, using molecular-based analysis, should enable a more accurate understanding of the clinical significance of various patterns of micrometastatic nodal disease. The establishment of metastasis to SLN might not be simply reflected by the flow dynamics of lymphatic fluid that drains from the primary site to the SLN, and the transportation of viable cancer cells. Recent studies have demonstrated that primary tumors can actively induce lymphangiogenesis and promote SLN metastasis. Moreover chemokine receptors in tumor cells may facilitate organ-specific tumor metastasis in many human cancers and some experimental models. In contrast, recent clinical and preclinical studies regard SLN as the first lymphoid organ to respond to tumor antigenic stimulation. SLN dramatically show morphological, phenotypical and functional changes that indicate immune suppression by tumor cells. The immune suppression in SLN results in failure of prevention or eradication of tumor metastasis. The mechanism of immunomodulation remains unclear; however, several regulatory molecules produced by tumor cells and tumor-associated macrophages or lymphocytes are likely to be responsible for inducing the immune suppression in SLN. Further studies may develop a novel immunotherapy that overcomes tumor-induced immune suppression and can prevent or eradicate SLN metastasis.
前哨淋巴结（SLN）被定义为首先接收来自原发性肿瘤部位淋巴引流的一个或多个淋巴结。对于大多数临床I/II期实体瘤，SLN的组织病理学状态是复发和总生存的最重要预测指标之一。分子技术的最新进展已证明SLN中存在微转移肿瘤细胞。现在有越来越多的数据支持SLN微转移在多种实体瘤中的临床相关性。使用基于分子的分析提高SLN中隐匿肿瘤细胞检测的灵敏度，应能更准确地理解各种微转移淋巴结疾病模式的临床意义。SLN转移的发生可能不仅仅由从原发部位引流到SLN的淋巴液流动动力学以及活癌细胞的运输所反映。最近的研究表明，原发性肿瘤可主动诱导淋巴管生成并促进SLN转移。此外肿瘤细胞中的趋化因子受体可能在许多人类癌症和一些实验模型中促进器官特异性肿瘤转移。相反，最近的临床和临床前研究将SLN视为第一个对肿瘤抗原刺激作出反应的淋巴器官。SLN显著表现出形态、表型和功能变化，表明肿瘤细胞的免疫抑制作用。SLN中的免疫抑制导致预防或根除肿瘤转移失败。免疫调节机制尚不清楚；然而，肿瘤细胞以及肿瘤相关巨噬细胞或淋巴细胞产生的几种调节分子可能是导致SLN免疫抑制的原因。进一步的研究可能会开发出一种新型免疫疗法，克服肿瘤诱导的免疫抑制并预防或根除SLN转移。
