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Tumor Hypoxia: A Key Determinant of Microenvironment Hostility and a Major Checkpoint during the Antitumor Response.
Critical Reviews in Immunology ( IF 0.8 ) Pub Date : 2018-01-01 , DOI: 10.1615/critrevimmunol.2019030168
Amirtharaj Francis 1 , Goutham Hassan Venkatesh 1 , Rania Faouzi Zaarour 1 , Nagwa Ahmed Zeinelabdin 1 , Hussam H Nawafleh 1 , Prathibha Prasad 1 , Stéphanie Buart 2 , Stéphane Terry 2 , Salem Chouaib 3
Affiliation  

Recent antitumor immunotherapies such as monoclonal antibodies targeting immune checkpoints have led to outstanding results in several cancers. However, despite the favorable outcomes for responding patients, the response rate remains relatively low. This is in part due to the influence of the tumor microenvironment (TME) in protecting the tumor from the antitumor immune response and facilitating immune escape. Tumor hypoxia is one of the most important features of the TME, exerting an adverse effect on tumor aggressiveness and patient prognosis. Hypoxic stress interferes with immune plasticity and promotes tumor heterogeneity and progression. Cellular adaptation to hypoxia is primarily mediated by a family of transcriptional regulators, hypoxia-inducible factor (HIF). Apart from hypoxia, the HIF pathway is modulated in a hypoxia-independent manner. HIF-1α stabilization and activity are regulated by epigenetic changes and mutations. Strong evidence indicates that tumor hypoxia controls malignant and metastatic phenotype of cancer cells and therefore presents a unique therapeutic challenge in the treatment of solid malignancies. An alluring alternative strategy to reinvigorate anticancer immune responses comes from the emerging field of TME and its associated pathways. Targeting hypoxia or its associated pathways may therefore offer new options in the design of innovative cancer immunotherapy approaches. In this article, we briefly review the potential of hypoxic stress on tumor plasticity and stromal reactivity as well as the possible targeting of hypoxia-induced pathways to increase immunotherapy efficiency.

中文翻译:

肿瘤缺氧:微环境敌意的关键决定因素和抗肿瘤反应过程中的主要检查点。

最近的抗肿瘤免疫疗法,例如靶向免疫检查点的单克隆抗体,已经在几种癌症中产生了杰出的结果。然而,尽管对反应患者有有利的结果,但反应率仍然相对较低。这部分是由于肿瘤微环境(TME)在保护肿瘤免受抗肿瘤免疫反应和促进免疫逃逸方面的影响。肿瘤缺氧是TME的最重要特征之一,对肿瘤的侵袭性和患者预后产生不利影响。低氧应激会干扰免疫可塑性并促进肿瘤异质性和进展。细胞对缺氧的适应性主要是由转录调节因子低氧诱导因子(HIF)家族介导的。除了缺氧 HIF途径以缺氧依赖性方式调节。HIF-1α的稳定和活性受表观遗传变化和突变的调节。有力的证据表明,肿瘤缺氧控制着癌细胞的恶性和转移表型,因此对实体恶性肿瘤的治疗提出了独特的治疗挑战。重振抗癌免疫反应的一种诱人的替代策略来自TME及其相关途径的新兴领域。因此,靶向缺氧或其相关途径可能为创新的癌症免疫治疗方法的设计提供新的选择。在本文中,我们简要回顾了低氧应激对肿瘤可塑性和基质反应性的潜在作用,以及针对低氧诱导的途径以提高免疫治疗效率的可能目标。HIF-1α的稳定和活性受表观遗传变化和突变的调节。有力的证据表明,肿瘤缺氧控制着癌细胞的恶性和转移表型,因此对实体恶性肿瘤的治疗提出了独特的治疗挑战。重振抗癌免疫反应的一种诱人的替代策略来自TME及其相关途径的新兴领域。因此,靶向缺氧或其相关途径可能为创新的癌症免疫治疗方法的设计提供新的选择。在本文中,我们简要回顾了低氧应激对肿瘤可塑性和基质反应性的潜在作用,以及针对低氧诱导的途径增加免疫治疗效率的可能目标。HIF-1α的稳定和活性受表观遗传变化和突变的调节。有力的证据表明,肿瘤缺氧控制着癌细胞的恶性和转移表型,因此对实体恶性肿瘤的治疗提出了独特的治疗挑战。重振抗癌免疫反应的一种诱人的替代策略来自TME及其相关途径的新兴领域。因此,靶向缺氧或其相关途径可能为创新的癌症免疫治疗方法的设计提供新的选择。在本文中,我们简要回顾了低氧应激对肿瘤可塑性和基质反应性的潜在作用,以及针对低氧诱导的途径以提高免疫治疗效率的可能目标。有力的证据表明,肿瘤缺氧控制着癌细胞的恶性和转移表型,因此对实体恶性肿瘤的治疗提出了独特的治疗挑战。重振抗癌免疫应答的一种诱人的替代策略来自新兴的TME领域及其相关途径。因此,靶向缺氧或其相关途径可能为创新的癌症免疫治疗方法的设计提供新的选择。在本文中,我们简要回顾了低氧应激对肿瘤可塑性和基质反应性的潜在作用,以及针对低氧诱导的途径以提高免疫治疗效率的可能目标。有力的证据表明,肿瘤缺氧控制着癌细胞的恶性和转移表型,因此对实体恶性肿瘤的治疗提出了独特的治疗挑战。重振抗癌免疫反应的一种诱人的替代策略来自TME及其相关途径的新兴领域。因此,靶向缺氧或其相关途径可能为创新的癌症免疫治疗方法的设计提供新的选择。在本文中,我们简要回顾了低氧应激对肿瘤可塑性和基质反应性的潜在作用,以及针对低氧诱导的途径以提高免疫治疗效率的可能目标。
更新日期:2019-11-01
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