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Adaptive immune resistance at the tumour site: mechanisms and therapeutic opportunities
Nature Reviews Drug Discovery ( IF 120.1 ) Pub Date : 2022-06-14 , DOI: 10.1038/s41573-022-00493-5
Tae Kon Kim 1, 2 , Esten N Vandsemb 3 , Roy S Herbst 2 , Lieping Chen 2, 4
Affiliation  

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-γ 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.



中文翻译:

肿瘤部位的适应性免疫抗性:机制和治疗机会

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抗性 (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 (PDL1)。通过抗体阻断 PDL1 与其受体 PD1 的结合(抗 PD 疗法)已导致一小部分晚期癌症患者的缓解,尤其是实体瘤患者。然而,许多将抗 PD 治疗与其他抗肿瘤药物相结合的临床试验在没有强有力的机械原理的情况下进行,未能确定协同或相加效应。在这篇透视文章中,

更新日期:2022-06-15
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