Department of Neurological Surgery, Feinberg School of Medicine, Northwestern University, 676 N St. Clair, Suite, Chicago, IL 60611, USA.
Northwestern Medicine Malnati Brain Tumor Institute of the Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
Cells. 2022 Mar 5;11(5):896. doi: 10.3390/cells11050896.
Polyamines are ubiquitous, amine-rich molecules with diverse processes in biology. Recent work has highlighted that polyamines exert profound roles on the mammalian immune system, particularly inflammation and cancer. The mechanisms by which they control immunity are still being described. In the context of inflammation and autoimmunity, polyamine levels inversely correlate to autoimmune phenotypes, with lower polyamine levels associated with higher inflammatory responses. Conversely, in the context of cancer, polyamines and polyamine biosynthetic genes positively correlate with the severity of malignancy. Blockade of polyamine metabolism in cancer results in reduced tumor growth, and the effects appear to be mediated by an increase in T-cell infiltration and a pro-inflammatory phenotype of macrophages. These studies suggest that polyamine depletion leads to inflammation and that polyamine enrichment potentiates myeloid cell immune suppression. Indeed, combinatorial treatment with polyamine blockade and immunotherapy has shown efficacy in pre-clinical models of cancer. Considering the efficacy of immunotherapies is linked to autoimmune sequelae in humans, termed immune-adverse related events (iAREs), this suggests that polyamine levels may govern the inflammatory response to immunotherapies. This review proposes that polyamine metabolism acts to balance autoimmune inflammation and anti-tumor immunity and that polyamine levels can be used to monitor immune responses and responsiveness to immunotherapy.
多胺是一种普遍存在的富含胺的分子，在生物学中有多种作用。最近的研究强调，多胺对哺乳动物的免疫系统，特别是炎症和癌症，发挥着深远的作用。它们控制免疫的机制仍在描述中。在炎症和自身免疫的背景下，多胺水平与自身免疫表型呈负相关，多胺水平越低，炎症反应越高。相反，在癌症的背景下，多胺和多胺生物合成基因与恶性程度呈正相关。在癌症中阻断多胺代谢会导致肿瘤生长减少，其作用似乎是通过增加 T 细胞浸润和巨噬细胞的促炎表型来介导的。这些研究表明，多胺耗竭会导致炎症，而多胺富集会增强髓样细胞的免疫抑制作用。事实上，多胺阻断和免疫疗法的联合治疗在癌症的临床前模型中显示出了疗效。考虑到免疫疗法的疗效与人类的自身免疫后遗症（称为免疫不良相关事件（iAREs））有关，这表明多胺水平可能控制对免疫疗法的炎症反应。这篇综述提出，多胺代谢作用是平衡自身免疫性炎症和抗肿瘤免疫的，并且多胺水平可以用于监测免疫反应和对免疫疗法的反应性。
