Refuge Biotechnologies, Inc., Menlo Park, CA, USA.
J Transl Med. 2021 Jan 6;19(1):9. doi: 10.1186/s12967-020-02667-4.
Over the last few years, cancer immunotherapy experienced tremendous developments and it is nowadays considered a promising strategy against many types of cancer. However, the exclusion of lymphocytes from the tumor nest is a common phenomenon that limits the efficiency of immunotherapy in solid tumors. Despite several mechanisms proposed during the years to explain the immune excluded phenotype, at present, there is no integrated understanding about the role played by different models of immune exclusion in human cancers. Hypoxia is a hallmark of most solid tumors and, being a multifaceted and complex condition, shapes in a unique way the tumor microenvironment, affecting gene transcription and chromatin remodeling. In this review, we speculate about an upstream role for hypoxia as a common biological determinant of immune exclusion in solid tumors. We also discuss the current state of ex vivo and in vivo imaging of hypoxic determinants in relation to T cell distribution that could mechanisms of immune exclusion and discover functional-morphological tumor features that could support clinical monitoring.
在过去的几年中，癌症免疫疗法取得了巨大的发展，如今被认为是对抗多种癌症的有前途的策略。然而，淋巴细胞从肿瘤巢中被排除是一种常见的现象，限制了免疫疗法在实体瘤中的效率。尽管多年来提出了几种机制来解释免疫排除表型，但目前对于不同的免疫排除模型在人类癌症中所起的作用还没有一个综合的认识。缺氧是大多数实体瘤的一个标志，并且作为一种多方面和复杂的情况，以独特的方式塑造肿瘤微环境，影响基因转录和染色质重塑。在这篇综述中，我们推测缺氧作为实体瘤中免疫排除的共同生物学决定因素具有上游作用。我们还讨论了目前关于缺氧决定因素的离体和在体成像与 T 细胞分布的关系，这可能有助于发现免疫排除的机制和发现支持临床监测的功能形态学肿瘤特征。
