Adaptive immune resistance at the tumour site: mechanisms and therapeutic opportunities
Adaptive immune resistance at the tumour site: mechanisms and therapeutic opportunities
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DOI：
10.1038/s41573-022-00493-5
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发表时间：
2022-06-14
影响因子：
120.1
通讯作者：
Chen, Lieping
中科院分区：
文献类型：
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作者：
Kim, Tae Kon;Vandsemb, Esten N.;Chen, Lieping
这篇透视文章讨论了肿瘤逃避免疫系统的机制，统称为适应性免疫抵抗（AIR），以及为什么在肿瘤微环境中定义AIR机制是免疫治疗开发的关键。肿瘤采用各种策略来适应并最终抵抗免疫攻击。这些机制统称为适应性免疫抵抗（AIR）。第一个定义和治疗验证的AIR机制是肿瘤中干扰素-γ选择性诱导程序性细胞死亡1配体1（PDL 1）。通过抗体阻断PDL 1与其受体PD 1的结合（抗PD治疗）已使一部分晚期癌症患者（尤其是实体瘤患者）缓解。然而，许多临床试验结合抗PD治疗与其他抗肿瘤药物进行没有强有力的机制的理由，未能确定协同或累加效应。在这篇透视文章中，我们讨论了为什么在肿瘤部位定义AIR机制应该是指导未来药物开发的关键焦点，以及改善当前癌症治疗的实用方法。
This Perspective article discusses the mechanisms used by tumours to evade the immune system, collectively called adaptive immune resistance (AIR), and why defining AIR mechanisms in the tumour microenvironment is key in immunotherapy development.Tumours employ various tactics to adapt and eventually resist immune attack. These mechanisms are collectively called adaptive immune resistance (AIR). The first defined and therapeutically validated AIR mechanism is the selective induction of programmed cell death 1 ligand 1 (PDL1) by interferon-gamma in the tumour. Blockade of PDL1 binding to its receptor PD1 by antibodies (anti-PD therapy) has resulted in remission of a fraction of patients with advanced-stage cancer, especially in solid tumours. However, many clinical trials combining anti-PD therapy with other antitumour drugs conducted without a strong mechanistic rationale have failed to identify a synergistic or additive effect. In this Perspective article, we discuss why defining AIR mechanisms at the tumour site should be a key focus to direct future drug development as well as practical approaches to improve current cancer therapy.