The interplay between the immune system and chemotherapy: emerging methods for optimizing therapy
The interplay between the immune system and chemotherapy: emerging methods for optimizing therapy
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DOI：
10.1586/1744666x.2014.865520
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发表时间：
2014-01-01
影响因子：
4.4
通讯作者：
Apetoh, Lionel
中科院分区：
文献类型：
--
作者：
Ghiringhelli, Francois;Apetoh, Lionel
临床前研究表明，免疫系统具有出人意料的能力，有助于化疗和放射治疗的成功。抗癌治疗可以通过促进死亡肿瘤细胞释放危险信号和/或消除免疫抑制细胞来触发免疫系统激活。然而，我们最近发现，一些化疗药物，如5-氟尿嘧啶和吉西他滨，在抗癌免疫反应中发挥了相互矛盾的作用。虽然5-氟尿嘧啶和Gem选择性地消除了荷瘤啮齿动物的髓系抑制细胞，但这些化疗药物促进了IL-1β的释放和促血管生成IL-17的CD4T细胞的发展。因此，应仔细考虑化疗对免疫反应的矛盾效应，以设计基于化疗和免疫调节剂的有效联合疗法。在这里，我们讨论了强调免疫系统在调节抗癌药物抗肿瘤疗效中的关键作用的初步发现如何开始转化为对人类的有效治疗。
Preclinical studies have revealed an unexpected ability of the immune system to contribute to the success of chemotherapy and radiotherapy. Anticancer therapies can trigger immune system activation by promoting the release of danger signals from dying tumor cells and/or the elimination of immunosuppressive cells. We have, however, recently discovered that some chemotherapies, such as 5-fluorouracil and gemcitabine, exert conflicting effects on anticancer immune responses. Although 5-fluorouracil and Gem selectively eliminated myeloid-derived suppressive cells in tumor-bearing rodents, these chemotherapies promoted the release of IL-1 beta and the development of pro-angiogenic IL-17-producing CD4 T cells. The ambivalent effects of chemotherapy on immune responses should thus be carefully considered to design effective combination therapies based on chemotherapy and immune modulators. Herein, we discuss how the initial findings underscoring the key role of the immune system in mediating the antitumor efficacy of anticancer agents could begin to translate into effective therapies in humans.