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免疫细胞的终身代谢适应性

Immune Cell Metabolic Fitness for Life.

作者信息

Bittman Kevin S

机构信息

Agilent Technologies, Inc., Santa Clara, CA 95051, USA.

出版信息

Antibodies (Basel). 2022 Apr 30;11(2):32. doi: 10.3390/antib11020032.

Abstract

Adoptive cell therapy holds great promise for treating a myriad of diseases, especially cancer. Within the last decade, immunotherapy has provided a significant leap in the successful treatment of leukemia. The research conducted throughout this period to understand the interrelationships between cancer cells and infiltrating immune cells winds up having one very common feature, bioenergetics. Cancer cells and immune cells both need ATP to perform their individual functions and cancer cells have adopted means to limit immune cell activity via changes in immune cell bioenergetics that redirect immune cell behavior to encourage tumor growth. Current leading strategies for cancer treatment super-charge an individual's own immune cells against cancer. Successful Chimeric Antigen Receptor T Cells (CAR T) target pathways that ultimately influence bioenergetics. In the last decade, scientists identified that mitochondria play a crucial role in T cell physiology. When modifying T cells to create chimeras, a unique mitochondrial fitness emerges that establishes stemness and persistence. This review highlights many of the key findings leading to this generation's CAR T treatments and the work currently being done to advance immunotherapy, to empower not just T cells but other immune cells as well against a variety of cancers.

摘要

过继性细胞疗法在治疗多种疾病,尤其是癌症方面具有巨大潜力。在过去十年中,免疫疗法在白血病的成功治疗上取得了重大飞跃。在此期间进行的旨在了解癌细胞与浸润免疫细胞之间相互关系的研究,最终都有一个非常共同的特征,即生物能量学。癌细胞和免疫细胞都需要ATP来执行各自的功能,并且癌细胞已采取手段通过改变免疫细胞生物能量学来限制免疫细胞活性,这种改变会使免疫细胞行为发生重定向,从而促进肿瘤生长。当前领先的癌症治疗策略是增强个体自身免疫细胞对抗癌症的能力。成功的嵌合抗原受体T细胞(CAR T)靶向最终影响生物能量学的途径。在过去十年中,科学家们发现线粒体在T细胞生理学中起着至关重要的作用。当对T细胞进行改造以产生嵌合体时,会出现一种独特的线粒体适应性,它决定了干性和持久性。这篇综述重点介绍了许多导致当今CAR T治疗的关键发现,以及目前为推进免疫疗法所做的工作,不仅增强T细胞,也增强其他免疫细胞对抗各种癌症的能力。

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