药学学报, 2019, 54(10): 1741-1748
引用本文:
徐骏, 耿美玉, 黄敏. 化疗药调控肿瘤免疫应答机制研究进展[J]. 药学学报, 2019, 54(10): 1741-1748.
XU Jun, GENG Mei-yu, HUANG Min. Mechanistic advancement in chemotherapeutic agents modulated antitumor immune response[J]. Acta Pharmaceutica Sinica, 2019, 54(10): 1741-1748.

化疗药调控肿瘤免疫应答机制研究进展
徐骏1,2, 耿美玉1,2, 黄敏1,2
1. 中国科学院上海药物研究所, 新药研究国家重点实验室, 上海 201203;
2. 中国科学院大学, 北京 100009
摘要:
化疗药即细胞毒类药物,主要通过影响肿瘤细胞DNA复制、转录和微管稳定性等对细胞增殖和存活至关重要的生物学事件,杀伤肿瘤细胞,是肿瘤药物治疗的传统手段。近年来,随着肿瘤免疫治疗在临床取得重大突破,化疗药因与免疫治疗潜在的联合用药空间,也迎来了新的发展契机。值得注意的是,化疗药对免疫系统的影响涉及免疫应答多个环节,作用广泛、机制复杂。当前,化疗药与肿瘤免疫联合治疗还较为随机,临床治疗获益尚不明确,亟需基于机制的理论指导。本文结合该领域的最新研究进展,从化疗药对免疫细胞的作用及对肿瘤细胞的免疫原性重塑这两方面,综述了化疗药调控肿瘤免疫应答的机制,特别就细胞死亡相关的免疫原性信号调控进行了详尽介绍。本文有望加深对化疗药肿瘤免疫调控的理解,并为探索化疗药的治疗空间提供理论指导。
关键词:    肿瘤      化疗      免疫应答      肿瘤微环境     
Mechanistic advancement in chemotherapeutic agents modulated antitumor immune response
XU Jun1,2, GENG Mei-yu1,2, HUANG Min1,2
1. State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China;
2. University of Chinese Academy of Sciences, Beijing 100009, China
Abstract:
Chemotherapeutic agents, also known as cytotoxic anticancer agents, inhibit the cancer cell proliferation via interrupting DNA replication, transcription and microtubule stability etc. Chemotherapeutic agents have been used in clinical cancer treatment for decades. Recently, with the tremendous advancement in immunooncology, chemotherapeutic agents have aroused renewed interest for their great potential to sensitize tumor cells to immunotherapy. Meanwhile, it is worth noting that the effects of chemotherapeutic agents on the immune system involve multiple aspects with complex mechanisms. Currently, there still lacks guidance for the combined use of chemotherapy and immunotherapy, and the clinical benefits remain obscure, impelling a better under-standing of the impact of chemotherapeutic agents on the antitumor immunity. This article reviews the mechanistic insights into chemotherapy-modulated antitumor immune responses, with major focus on the direct effect on immune cells and the immunogenic remodeling of tumor cells. The review is particularly interested in the chemo-therapy-trigged signaling that contributes to the immunogenic cell death. This review may provide useful insights into the immunomodulatory effects of chemotherapeutic agents and the implications in exploring therapeutic oppor-tunities of chemotherapy in cancer immunotherapy.
Key words:    tumor    chemotherapy    immune response    tumor immune microenvironment   
收稿日期: 2019-07-31
DOI: 10.16438/j.0513-4870.2019-0617
基金项目: 中国科学院战略性先导科技专项(XDA12020102).
通讯作者: 黄敏,Tel/Fax:86-21-50806722,E-mail:mhuang@simm.ac.cn
Email: mhuang@simm.ac.cn
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