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CCR4是CC趋化因子受体(CC chemokine receptor,CCR)家族中的一员,主要表达于多种淋巴细胞。其高亲和力配体为胸腺和活化调节的趋化因子(thymus and activation regulated chemokine,TARC/CCL17)及巨噬细胞衍生的趋化因子(macrophage-derived chemokine,MDC/CCL22/STCP-1)。CCR4主要通过CCR4+Treg细胞及CCR4+Th2细胞发挥免疫效应。CCR4的高表达与多种血液系统肿瘤以及恶性实体瘤的浸润和预后相关,其机制为Treg细胞表面的CCR4通过与其配体TARC、MDC的结合趋化Treg细胞,引起免疫逃逸,从而导致不良临床后果。多种恶性肿瘤转移模型的研究进一步揭示了CCR4与恶性肿瘤转移之间的关系。抗CCR4嵌合型单克隆抗体KM2760的研究已进入Ⅱ期临床试验阶段,阻断TARC/MDC-CCR4信号通路,有可能成为恶性肿瘤分子靶向治疗的新策略。
CCR4 is a member of CC chemokine receptor (CCR) family and is mainly expressed in various lymphocytes. Its high-affinity ligands are thymus and activation regulated chemokine (TARC / CCL17) and macrophage-derived chemokine (MDC / CCL22 / STCP-1). CCR4 exerts an immune effect mainly through CCR4 + Treg cells and CCR4 + Th2 cells. The high expression of CCR4 is associated with a variety of hematological and malignant solid tumor infiltration and prognosis through the mechanism that CCR4 on the surface of Treg cells chemotactic to Treg cells by binding to its ligands TARC and MDC leading to immune escape resulting in poor clinical as a result of. A variety of malignant tumor metastasis models further reveal the relationship between CCR4 and malignant tumor metastasis. The study of anti-CCR4 chimeric monoclonal antibody KM2760 has entered phase Ⅱ clinical trials, blocking the TARC / MDC-CCR4 signaling pathway may become a new strategy for molecular targeted therapy of malignant tumors.