Pals Steven T, de Gorter David J J, Spaargaren Marcel
Department of Pathology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands.
Blood. 2007 Nov 1;110(9):3102-11. doi: 10.1182/blood-2007-05-075176. Epub 2007 Jul 26.
The orchestration of systemic immune responses is critically dependent on coordinated lymphocyte migration and recirculation. This "homing" guides lymphocytes to the microenvironments that control their differentiation and survival, disperses the immunologic repertoire, and targets effector lymphocytes to sites of antigenic insult. Lymphocyte homing is a multistep process that requires chemotaxis and cell adhesion coupled with strategies to overcome physical barriers. At the molecular level, it is regulated by adhesion molecules and chemokines, and facilitated by intrinsic molecular programs that allow "ameboid" shape change, allowing highly effective lymphocyte traffic between different tissue compartments. In case of malignant transformation, however, the fact that lymphocytes are "licensed to move" forms a serious threat to the organism, because it permits rapid tumor dissemination irrespective of the conventional anatomic boundaries limiting early spread in most types of cancer. Thus, unlike the metastatic spread of other cancers, lymphoma dissemination generally is not a reflection of tumor progression but of conserved physiological behavior. The dissemination patterns often reflect basic rules of lymphocyte homing, explaining the strikingly tissue-specific dissemination of, for example, mucosal lymphomas, cutaneous lymphomas, and multiple myeloma. Understanding the molecular mechanisms underlying this behavior may provide novel targets for treatment of lymphoma patients.
全身免疫反应的协调运作严重依赖于淋巴细胞的协同迁移和再循环。这种“归巢”引导淋巴细胞进入控制其分化和存活的微环境，分散免疫库，并将效应淋巴细胞靶向抗原攻击部位。淋巴细胞归巢是一个多步骤过程，需要趋化作用和细胞黏附以及克服物理屏障的策略。在分子水平上，它由黏附分子和趋化因子调节，并由允许“变形虫样”形状改变的内在分子程序促进，从而使淋巴细胞在不同组织隔室之间进行高效运输。然而，在发生恶性转化时，淋巴细胞“被许可移动”这一事实对机体构成了严重威胁，因为它允许肿瘤迅速扩散，而不受大多数类型癌症中限制早期扩散的传统解剖边界的约束。因此，与其他癌症的转移扩散不同，淋巴瘤的扩散通常不是肿瘤进展的反映，而是保守生理行为的体现。其扩散模式常常反映淋巴细胞归巢的基本规律，这解释了例如黏膜淋巴瘤、皮肤淋巴瘤和多发性骨髓瘤明显的组织特异性扩散现象。了解这种行为背后的分子机制可能为淋巴瘤患者的治疗提供新的靶点。
