Dating back to the seminal work of Paul Ehrlich, the idea of harnessing our immune system to eliminate cancerous cells is now over a century old. In the presence of a functional immune system that so efficiently guards the host against developing neoplasms, tumour cells must evolve sophisticated strategies to escape immune destruction in order to give rise to clinically detectable cancers. A new way of treating cancer would thus be to target the immune system itself rather than the tumour, and extensive studies in randomised trials have cemented the possibility of using immunotherapy for treating advanced-stage cancers. Immunotherapy, however, is only tolerated in a minority of patients and in many cases, patients suffer from adverse immune-related reactions when the immune system goes into overdrive. A primary barrier thwarting the development of effective immunotherapy seems to coalesce into the peculiarities of the tumour microenvironment for which hypoxia is a key feature. Here, we review emerging themes on how hypoxia contributes to immune suppression and obstructs anti-tumour effector cell functions. We discuss the challenges and opportunities relating to the potential for dually targeting hypoxia and the immune system to promote durable and favourable responses in cancer patients.

追溯到保罗·埃里希（Paul Ehrlich）的开创性工作，利用我们的免疫系统消除癌细胞的想法已经有一百多年的历史了。在功能性免疫系统的存在下，它能有效地保护宿主免受肿瘤侵袭，肿瘤细胞必须进化出复杂的策略来逃避免疫破坏，从而产生可临床检测的癌症。因此，治疗癌症的一种新方法将针对免疫系统本身而不是肿瘤，并且随机试验中的大量研究巩固了使用免疫疗法治疗晚期癌症的可能性。然而，免疫疗法仅在少数患者中可以接受，并且在许多情况下，当免疫系统过度运转时，患者会遭受与免疫相关的不良反应。阻碍有效免疫疗法发展的主要障碍似乎是肿瘤微环境的特殊性，缺氧是其关键特征。在这里，我们回顾了有关缺氧如何促进免疫抑制并阻碍抗肿瘤效应细胞功能的新兴主题。我们讨论了潜在的挑战和机遇，这些挑战和机遇涉及双重靶向缺氧和免疫系统，以促进癌症患者持久和良好的反应。