Department of Medical Oncology and Immunology, Nagoya City University Graduate School of Medical Sciences, Mizuho-ku, Nagoya, Japan.
Cancer Sci. 2011 Jan;102(1):44-50. doi: 10.1111/j.1349-7006.2010.01767.x. Epub 2010 Nov 2.
Evading immune surveillance is one of the common hallmarks of cancer. Herein we describe two major evasion mechanisms in lymphoma, focusing on regulatory T (Treg) cells and C-C chemokine receptor 4 (CCR4) expressed on these cells. First, the tumor cells themselves function as Treg cells, characterized by expression of CCR4, contributing to tumor survival by downregulating host immunity. Second, CCR4 ligands are produced by tumor cells, which attract other CCR4(+) Treg cells to the vicinity of the tumor. CCR4(+) adult T-cell leukemia//lymphoma is an example of the former phenomenon, and Hodgkin lymphoma of the latter, for which an almost identical immunopathogenesis has been reported in many types of cancer. Awareness of the importance of CCR4 allows the rational design of more effective cancer treatments. Accordingly, we have developed a defucosylated anti-CCR4 mAb, the first therapeutic agent targeting CCR4 to be used clinically for cancer. The therapeutic anti-CCR4 mAb represents a promising treatment method for patients with CCR4(+) neoplasms by directly killing the cancer cells, but could also be used as a novel treatment strategy for many types of CCR4(-) cancers to overcome the suppressive effect of CCR4(+) Treg cells.
逃避免疫监视是癌症的共同特征之一。在此，我们描述了淋巴瘤中的两种主要逃避机制，重点是调节性 T (Treg) 细胞和这些细胞上表达的 C-C 趋化因子受体 4 (CCR4)。首先，肿瘤细胞本身作为 Treg 细胞发挥作用，其特征是表达 CCR4，通过下调宿主免疫来促进肿瘤存活。其次，肿瘤细胞产生 CCR4 配体，吸引其他 CCR4(+)Treg 细胞到肿瘤附近。CCR4(+)成人 T 细胞白血病/淋巴瘤是前者的一个例子，霍奇金淋巴瘤则是后者的一个例子，许多类型的癌症都报道了几乎相同的免疫发病机制。认识到 CCR4 的重要性可以为更有效的癌症治疗提供合理的设计。因此，我们开发了一种去岩藻糖基化的抗 CCR4 mAb，这是第一种用于癌症临床的靶向 CCR4 的治疗性抗体。治疗性抗 CCR4 mAb 通过直接杀死癌细胞，为 CCR4(+)肿瘤患者提供了一种有前途的治疗方法，但也可用于许多 CCR4(-)癌症类型的新型治疗策略，以克服 CCR4(+)Treg 细胞的抑制作用。
