Cisplatin-induced antitumor immunomodulation: a review of preclinical and clinical evidence.
Cisplatin-induced antitumor immunomodulation: a review of preclinical and clinical evidence.
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DOI：
10.1158/1078-0432.ccr-14-1298
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发表时间：
2014-11-01
期刊：
影响因子：
--
通讯作者：
Adusumilli PS
中科院分区：
文献类型：
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作者：
de Biasi AR;Villena-Vargas J;Adusumilli PS
与长期以来认为化疗是免疫抑制的观点相反，新出现的证据表明顺铂的抗癌活性不仅限于其抑制有丝分裂的能力，而且顺铂还具有重要的免疫调节作用。因此，我们系统地研究了相关的临床前文献，并确定了顺铂诱导的抗肿瘤免疫调节的四种主要机制：（1）MHC I类表达上调;（2）效应细胞的募集和增殖;（3）细胞毒性效应物的裂解活性上调;（4）免疫抑制微环境下调。基于顺铂的联合化疗的抗肿瘤免疫调节作用也开始在临床上得到利用;因此，我们还审查了适用的临床文献，并讨论了监测免疫系统的各种组成部分（及其对顺铂的反应）如何为疾病监测和诊断增加新的复杂程度。总之，越来越多的关于顺铂诱导的抗肿瘤免疫调节的文献最终突出了联合收割机传统化疗与免疫治疗相结合的协同策略的治疗潜力。
Contrary to the long held belief that chemotherapy is immunosuppressive, emerging evidence indicates that the anticancer activity of cisplatin is not limited to its ability to inhibit mitosis, but that cisplatin also has important immunomodulatory effects. We therefore methodically examined the relevant preclinical literature and identified four main mechanisms of cisplatin-induced antitumor immunomodulation: (1) MHC class I expression upregulation; (2) recruitment and proliferation of effector cells; (3) upregulation of the lytic activity of cytotoxic effectors; and (4) downregulation of the immunosuppressive microenvironment. Cisplatin-based combination chemotherapy’s antitumor immunomodulatory effects are also beginning to be harnessed in the clinic; we therefore additionally reviewed the applicable clinical literature and discussed how monitoring various components of the immune system (and their responses to cisplatin) can add new levels of sophistication to disease monitoring and prognostication. In summation, this growing body of literature on cisplatin-induced antitumor immunomodulation ultimately highlights the therapeutic potential of synergistic strategies that combine traditional chemotherapy with immunotherapy.