Institute of Cancer Therapeutics, University of Bradford; Bradford BD7 1DP, United Kingdom.
Faculty of Pharmacy, Zarqa University, PO Box 132222, Zarqa 13132, Jordan.
Biochim Biophys Acta Rev Cancer. 2021 Jan;1875(1):188499. doi: 10.1016/j.bbcan.2020.188499. Epub 2020 Dec 29.
The CCR7 chemokine axis is comprised of chemokine ligand 21 (CCL21) and chemokine ligand 19 (CCL19) acting on chemokine receptor 7 (CCR7). This axis plays two important but apparently opposing roles in cancer. On the one hand, this axis is significantly engaged in the trafficking of a number of effecter cells involved in mounting an immune response to a growing tumour. This suggests therapeutic strategies which involve potentiation of this axis can be used to combat the spread of cancer. On the other hand, the CCR7 axis plays a significant role in controlling the migration of tumour cells towards the lymphatic system and metastasis and can thus contribute to the expansion of cancer. This implies that therapeutic strategies which involve decreasing signaling through the CCR7 axis would have a beneficial effect in preventing dissemination of cancer. This dichotomy has partly been the reason why this axis has not yet been exploited, as other chemokine axes have, as a therapeutic target in cancer. Recent report of a crystal structure for CCR7 provides opportunities to exploit this axis in developing new cancer therapies. However, it remains unclear which of these two strategies, potentiation or antagonism of the CCR7 axis, is more appropriate for cancer therapy. This review brings together the evidence supporting both roles of the CCR7 axis in cancer and examines the future potential of each of the two different therapeutic approaches involving the CCR7 axis in cancer.
CCR7 趋化因子轴由趋化因子配体 21（CCL21）和趋化因子配体 19（CCL19）作用于趋化因子受体 7（CCR7）组成。该轴在癌症中发挥着两个重要但明显相反的作用。一方面，该轴显著参与了许多效应细胞向生长肿瘤的免疫反应的运输。这表明，涉及增强该轴的治疗策略可以用于对抗癌症的扩散。另一方面，CCR7 轴在控制肿瘤细胞向淋巴系统和转移的迁移中起着重要作用，因此有助于癌症的扩张。这意味着，涉及减少 CCR7 轴信号传导的治疗策略在预防癌症传播方面将产生有益的效果。这种二分法部分是为什么这个轴尚未像其他趋化因子轴那样被用作癌症治疗的治疗靶点的原因之一。最近关于 CCR7 晶体结构的报告为开发新的癌症治疗方法提供了利用该轴的机会。然而，目前尚不清楚这两种策略，即增强或拮抗 CCR7 轴，哪种更适合癌症治疗。这篇综述汇集了支持 CCR7 轴在癌症中的两种作用的证据，并探讨了涉及 CCR7 轴的两种不同治疗方法在癌症中的未来潜力。
