靶向CCL21/CCR7轴治疗肿瘤转移的研究进展

Progress in targeting therapy of cancer metastasis by CCL21/CCR7 axis

摘要:

转移是肿瘤患者死亡最常见的原因，而淋巴转移是大多数肿瘤转移的主要途径之一。近年来，CC趋化因子配体21 (CC chemokine ligand 21，CCL21) 及其受体CC趋化因子受体7型 (CC chemokine receptor type 7，CCR7) 在淋巴转移中的作用逐渐受到关注。CCL21主要由淋巴内皮细胞产生，其与树突状细胞 (Dendritic cells，DCs) 和T细胞等表面CCR7的相互作用是免疫细胞淋巴迁移及淋巴结归巢的主要决定因素。然而，表达CCR7的肿瘤细胞也可以利用类似的机制进入淋巴管进行淋巴转移。如何靶向CCL21/CCR7轴，既能抑制淋巴转移，又不影响抗肿瘤免疫反应已成为肿瘤免疫治疗研究的重要议题。文中将对CCL21/CCR7轴在淋巴转移中的作用及其作为靶点治疗肿瘤转移的临床前和临床试验研究进行综述，为靶向CCL21/CCR7信号轴治疗肿瘤转移的相关研究提供参考。

Abstract:

Metastasis is the leading cause of mortality for cancer patients, and lymphatic metastasis is one of the main ways of tumor metastasis. The role of CCL21 and its receptor CCR7 in lymphatic metastasis has been increasingly concerned in recent years. CCR7 is mainly expressed by both dendritic cells and T cells for immune responses. CCL21, the chemokine ligand for CCR7, secreted from lymphatic endothelial cells binds CCR7 and recruits immune cells toward lymphatic vessels and lymphatic nodes. CCR7 expressed tumor cells can also metastasize to lymphatic system by the similar way as immune cells. Targeting CCL21/CCR7 axis to inhibit lymphatic metastasis but remain potent anti-tumor immune response has increasingly become a spot light of tumor immunotherapy. In this review, we summarize the role of CCL21/CCR7 axis in lymphatic metastasis, as well as preclinical trials and clinical trials in targeting CCL21/CCR7 axis for tumor metastasis therapy, hoping to accelerate the progress on tumor metastasis therapy by targeting CCL21/CCR7 axis.