癌症中的多胺：整合有机体代谢和抗肿瘤免疫

2022-05-17 12:18

这篇前瞻性文章的目的是向读者介绍多胺、多胺代谢、微生物群和饮食相互联系以建立促进癌症发生和发展的肿瘤微环境的多种方式。

Polyamines in cancer: integrating organismal metabolism and antitumour immunity

（Nat Rev Cancer；IF:60.716）

Holbert CE, Cullen MT, Casero RA Jr, Stewart TM. Polyamines in cancer: integrating organismal metabolism and antitumour immunity [published online ahead of print, 2022 Apr 27]. Nat Rev Cancer. 2022

Abstract |

The natural mammalian polyamines putrescine, spermidine and spermine are essential for both normal and neoplastic cell function and replication. Dysregulation of metabolism of polyamines and their requirements is common in many cancers. Both clinical and experimental depletion of polyamines have demonstrated their metabolism to be a rational target for therapy; however, the mechanisms through which polyamines can establish a tumour-permissive microenvironment are only now emerging. Recent data indicate that polyamines can play a major role in regulating the antitumour immune response, thus likely contributing to the existence of immunologically 'cold' tumours that do not respond to immune checkpoint blockade. Additionally, the interplay between the microbiota and associated tissues creates a tumour microenvironment in which polyamine metabolism, content and function can all be dramatically altered on the basis of microbiota composition, dietary polyamine availability and tissue response to its surrounding microenvironment. The goal of this Perspective is to introduce the reader to the many ways in which polyamines, polyamine metabolism, the microbiota and the diet interconnect to establish a tumour microenvironment that facilitates the initiation and progression of cancer. It also details ways in which polyamine metabolism and function can be successfully targeted for therapeutic benefit, including specifically enhancing the antitumour immune response.

自然界中哺乳动物的多胺腐胺、亚精胺和精胺对于正常和肿瘤细胞的功能和复制都是必不可少的。多胺代谢失调及其需求在许多癌症中都很常见。不论是在临床还是实验中，多胺的消耗都显示其代谢过程是一个合理的治疗靶点；然而，多胺能够建立肿瘤许可的微环境这一机制仅仅是最近的发现。最近的数据表明，多胺可以在调节抗肿瘤免疫反应中发挥重要作用，因此可能对免疫检查点抑制剂欠反应的免疫“冷”肿瘤有促进作用。此外，微生物群和相关组织之间的相互作用创造了一个肿瘤微环境，其中多胺代谢、含量和功能都可以根据微生物群组成、膳食多胺可用性和组织对其周围微环境的反应而发生显著改变。这篇前瞻性文章的目的是向读者介绍多胺、多胺代谢、微生物群和饮食相互联系以建立促进癌症发生和发展的肿瘤微环境的多种方式。它还详细介绍了能够成功靶向多胺代谢及其功能的方法，以期带来治疗获益，其中包括特异性增强抗肿瘤免疫反应。