Immunotherapy is poised to become an increasingly utilized therapy in the treatment of cancer. However, several abnormalities in the tumor microenvironment (TME) that can thwart the efficacy of immunotherapies have been established. Microenvironmental hypoxia is a determining factor in shaping aggressiveness, metastatic potential and treatment resistance of solid tumors. The characterization of this phenomenon could prove beneficial for determining a patient’s treatment path and for the introduction of novel targetable factors that can enhance therapeutic outcome. Indeed, the ablation of hypoxia has the potential to sensitize tumors to immunotherapy by metabolically remodeling their microenvironment. In this review, we discuss the intrinsic contributions of hypoxia to cellular plasticity, heterogeneity, stemness and genetic instability in the context of immune escape. In addition, we will shed light on how managing hypoxia can ameliorate response to immunotherapy and how integrating hypoxia gene signatures could play a role in this pursuit.

免疫疗法有望成为治疗癌症的一种越来越广泛使用的疗法。然而，已经建立了可以阻止免疫疗法功效的肿瘤微环境（TME）中的几种异常。微环境缺氧是决定实体瘤的侵略性，转移潜力和治疗抵抗力的决定性因素。这种现象的特征可能证明对确定患者的治疗途径以及引入可增强治疗效果的新型靶向因子有益。的确，缺氧的消融有可能通过代谢性改造其微环境使肿瘤对免疫治疗敏感。在这篇评论中，我们讨论了缺氧对细胞可塑性，异质性，免疫逃逸情况下的茎干和遗传不稳定性。此外，我们将阐明如何处理缺氧可以改善对免疫疗法的反应，以及整合缺氧基因标记如何在这种追求中发挥作用。