Institute for Translational Medicine, The Affiliated Hospital, College of medicine, Qingdao University, Qingdao, China.
School of Basic Medical Sciences, College of medicine, Qingdao University, Qingdao, China.
Theranostics. 2020 Jul 23;10(20):9214-9229. doi: 10.7150/thno.45125. eCollection 2020.
Cancer is a leading cause of mortality and morbidity worldwide. Despite major improvements in current therapeutic methods, ideal therapeutic strategies for improved tumor elimination are still lacking. Recently, immunotherapy has attracted much attention, and many immune-active agents have been approved for clinical use alone or in combination with other cancer drugs. However, some patients have a poor response to these agents. New agents and strategies are needed to overcome such deficiencies. Phosphatidylserine (PS) is an essential component of bilayer cell membranes and is normally present in the inner leaflet. In the physiological state, PS exposure on the external leaflet not only acts as an engulfment signal for phagocytosis in apoptotic cells but also participates in blood coagulation, myoblast fusion and immune regulation in nonapoptotic cells. In the tumor microenvironment, PS exposure is significantly increased on the surface of tumor cells or tumor cell-derived microvesicles, which have innate immunosuppressive properties and facilitate tumor growth and metastasis. To date, agents targeting PS have been developed, some of which are under investigation in clinical trials as combination drugs for various cancers. However, controversial results are emerging in laboratory research as well as in clinical trials, and the efficiency of PS-targeting agents remains uncertain. In this review, we summarize recent progress in our understanding of the physiological and pathological roles of PS, with a focus on immune suppressive features. In addition, we discuss current drug developments that are based on PS-targeting strategies in both experimental and clinical studies. We hope to provide a future research direction for the development of new agents for cancer therapy.
癌症是全球范围内导致死亡和发病的主要原因。尽管目前的治疗方法有了重大改进，但仍缺乏理想的治疗策略以提高肿瘤消除率。最近，免疫疗法引起了广泛关注，许多免疫活性药物已被批准单独或与其他癌症药物联合用于临床。然而，一些患者对这些药物的反应不佳。需要新的药物和策略来克服这些缺陷。磷脂酰丝氨酸 (PS) 是双层细胞膜的重要组成部分，通常存在于内层。在生理状态下，PS 在外层的暴露不仅作为凋亡细胞吞噬作用的吞噬信号，还参与非凋亡细胞中的血液凝固、成肌细胞融合和免疫调节。在肿瘤微环境中，肿瘤细胞或肿瘤细胞衍生的微泡表面 PS 的暴露显著增加，这些微泡具有先天的免疫抑制特性，促进肿瘤生长和转移。迄今为止，已经开发出针对 PS 的药物，其中一些正在临床试验中作为各种癌症的联合药物进行研究。然而，实验室研究和临床试验中都出现了有争议的结果，PS 靶向药物的效率仍不确定。在这篇综述中，我们总结了 PS 的生理和病理作用的最新研究进展，重点介绍其免疫抑制特征。此外，我们还讨论了基于 PS 靶向策略的当前药物开发在实验和临床研究中的情况。我们希望为癌症治疗新药物的开发提供未来的研究方向。
