A decade of checkpoint blockade immunotherapy in melanoma: understanding the molecular basis for immune sensitivity and resistance.

A decade of checkpoint blockade immunotherapy in melanoma: understanding the molecular basis for immune sensitivity and resistance.
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黑色素瘤中的十年检查点阻断免疫疗法:了解免疫敏感性和抗性的分子基础。

DOI:
10.1038/s41590-022-01141-1
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发表时间:
2022-05
期刊:
影响因子:
30.5
通讯作者:
Zappasodi, Roberta
Zappasodi, Roberta
中科院分区:
医学1区
文献类型:
--
作者:
Huang, Alexander C.;Zappasodi, Roberta

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免疫检查点抑制剂ipilimumab被批准用于晚期黑色素瘤已有十年,现在是时候反思有关调节免疫系统治疗癌症的经验教训,以及进一步扩展当前和新兴免疫疗法疗效的新方法。在这里,我们回顾了导致我们目前了解人类黑色素瘤免疫微环境的研究以及支持这些观察结果的机制工作。我们讨论了这些信息如何指导更精确地分析免疫检查点阻断和新型免疫方法的作用机制。最后,我们回顾了支持黑色素瘤代谢适应对抗肿瘤免疫的负面影响的新证据,并讨论了如何抵消这种机制,以更成功地使用免疫治疗。
Ten years since the immune checkpoint inhibitor ipilimumab was approved for advanced melanoma, it is time to reflect on the lessons learned regarding modulation of the immune system to treat cancer and on novel approaches to further extend the efficacy of current and emerging immunotherapies. Here, we review the studies that led to our current understanding of the melanoma immune microenvironment in humans and the mechanistic work supporting these observations. We discuss how this information is guiding more precise analyses of the mechanisms of action of immune checkpoint blockade and novel immunotherapeutic approaches. Lastly, we review emerging evidence supporting the negative impact of melanoma metabolic adaptation on anti-tumor immunity and discuss how to counteract such mechanisms for more successful use of immunotherapy.
DOI: 10.1126/sciimmunol.abc2728
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影响因子: 24.8
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