Chemokine Receptor-Targeted Therapies: Special Case for CCR8.
Chemokine Receptor-Targeted Therapies: Special Case for CCR8.
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DOI：
10.3390/cancers14030511
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发表时间：
2022-01-20
期刊：
影响因子：
5.2
通讯作者：
Moser B
中科院分区：
文献类型：
--
作者：
Moser B
针对所谓的免疫检查点分子的抗体代表了癌症治疗的实质性改进。这些生物试剂突出了癌症和我们自己的免疫系统之间的微妙相互作用。癌症的进展是通过在肿瘤内建立一个抑制性免疫细胞隔间来实现的。因此，消除这些抑制细胞是一种有吸引力的策略，以增强有益的抗肿瘤免疫，并进一步改进新建立的免疫检查点治疗。本文就CCR8作为一种高表达于抑制性免疫细胞上的趋化因子受体及其作为肿瘤治疗新靶点的潜在价值作一综述。针对细胞毒性T淋巴细胞相关蛋白-4(CTLA-4)和程序性死亡受体-1(PD-1)或其配体-1(PD-L1)的免疫检查点阻断抑制物(CBIS)已经改变了许多癌症患者的面貌。从翻译的角度来看，这一显著的进展突显了免疫细胞在控制肿瘤进展中的重要性。由于目前的CBI疗法只惠及少数患者，因此仍有改进的空间。此外，对免疫检查点受体的干扰经常导致免疫相关不良事件(IrAEs)，在一些患者中会有危及生命的后果。肿瘤微环境(TME)中的免疫抑制细胞，包括肿瘤内调节性T细胞(Treg)、肿瘤相关巨噬细胞(TAMs)和髓系来源抑制细胞(MDSCs)，有助于肿瘤的进展并与负面疾病前景相关。最近的报道揭示了趋化因子受体CCR8在肿瘤Treg细胞上的选择性表达，使CCR8成为翻译研究的一个有前途的靶点。在这篇综述中，我总结了我们目前对CCR8在生理和病理生理过程中的细胞分布和功能的了解。讨论包括评估去除表达CCR8的细胞可能如何影响远程部位的抗肿瘤免疫和免疫动态平衡。基于这些考虑，CCR8似乎是未来翻译研究中一个有前途的新目标。
Antibodies directed at so-called immune checkpoint molecules represent a substantial improvement in cancer therapy. These biological reagents highlight the exquisite interplay between cancer and our own immune system. Cancer progression is enabled by establishing a compartment of suppressive immune cells within the tumor. Therefore, elimination of these suppressor cells is an attractive strategy to augment beneficial anti-tumor immunity and to further improve the newly established immune checkpoint therapy. This review focuses on CCR8, a chemokine receptor highly expressed on suppressive immune cells, and its potential value as a novel target in cancer therapy. Immune checkpoint blockade inhibitors (CBIs) targeting cytotoxic T lymphocyte associated protein-4 (CTLA-4) and program death receptor-1 (PD-1) or its ligand-1 (PD-L1) have transformed the outlook of many patients with cancer. This remarkable progress has highlighted, from the translational point of view, the importance of immune cells in the control of tumor progression. There is still room for improvement, since current CBI therapies benefit a minority of patients. Moreover, interference with immune checkpoint receptors frequently causes immune related adverse events (irAEs) with life-threatening consequences in some of the patients. Immunosuppressive cells in the tumor microenvironment (TME), including intratumoral regulatory T (Treg) cells, tumor-associated macrophages (TAMs) and myeloid-derived suppressor cells (MDSCs), contribute to tumor progression and correlate with a negative disease outlook. Recent reports revealed the selective expression of the chemokine receptor CCR8 on tumor Treg cells, making CCR8 a promising target in translational research. In this review, I summarize our current knowledge about the cellular distribution and function of CCR8 in physiological and pathophysiological processes. The discussion includes an assessment of how the removal of CCR8-expressing cells might affect both anti-tumor immunity as well as immune homeostasis at remote sites. Based on these considerations, CCR8 appears to be a promising novel target to be considered in future translational research.
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DOI：
10.1158/1078-0432.ccr-12-2091
发表时间：
2013-04-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Eruslanov E;Stoffs T;Kim WJ;Daurkin I;Gilbert SM;Su LM;Vieweg J;Daaka Y;Kusmartsev S
通讯作者：
Kusmartsev S
DOI：
10.1084/jem.20201329
发表时间：
2021-06-07
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Bhatt D;Kang B;Sawant D;Zheng L;Perez K;Huang Z;Sekirov L;Wolak D;Huang JY;Liu X;DeVoss J;Manzanillo PS;Pierce N;Zhang Z;Symons A;Ouyang W
通讯作者：
Ouyang W
影响因子：
11.2
作者：
Campbell, Joseph R.;McDonald, Bryan R.;Lan, Ruth Y.
通讯作者：
Lan, Ruth Y.
影响因子：
24.8
作者：
Ahmadzadeh, Mojgan;Pasetto, Anna;Rosenberg, Steven A.
通讯作者：
Rosenberg, Steven A.
影响因子：
32.4
作者：
Delacher, Michael;Imbusch, Charles D.;Feuerer, Markus
通讯作者：
Feuerer, Markus