Metabolism of immune cells in cancer.

Metabolism of immune cells in cancer.
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DOI:
10.1038/s41568-020-0273-y
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发表时间:
2020-09
期刊:
Nature reviews. Cancer
影响因子:
--
通讯作者:
Powell JD
Powell JD
中科院分区:
其他
文献类型:
--
作者:
Leone RD;Powell JD

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通过检查点阻断和过继细胞疗法的成功,免疫疗法已成为癌症的既定治疗方式。细胞代谢已成为癌细胞和免疫细胞的生存力和功能的关键决定因素。为了维持巨大的合成代谢需求,肿瘤采用了不同于未转化体细胞的专门代谢。这种代谢导致肿瘤微环境通常是酸性的,缺氧的和/或缺乏免疫细胞所需的关键营养素。在这种情况下,肿瘤代谢本身是一个检查点,可以限制免疫介导的肿瘤破坏。由于我们对免疫细胞代谢和癌症代谢的理解在过去十年中显着增长,我们正处于能够以治疗上有意义的方式解开癌细胞代谢和免疫代谢相互作用的尖端。虽然有一些代谢过程似乎对癌症和免疫细胞都很重要,但代谢的异质性和可塑性可能有助于区分两者。因此,理解构成对癌症的免疫应答的不同细胞的不同代谢要求提供了选择性调节免疫细胞功能的机会。对癌症和免疫代谢的这种细致入微的评估可以揭示代谢脆弱性和治疗窗口,从而干预增强的免疫治疗。
Through the successes of checkpoint blockade and adoptive cellular therapy, immunotherapy has become an established treatment modality for cancer. Cellular metabolism has emerged as a critical determinant of the viability and function of both cancer cells and immune cells. In order to sustain prodigious anabolic needs, tumours employ a specialized metabolism that differs from untransformed somatic cells. This metabolism leads to a tumour microenvironment that is commonly acidic, hypoxic and/or depleted of critical nutrients required by immune cells. In this context, tumour metabolism itself is a checkpoint that can limit immune-mediated tumour destruction. Because our understanding of immune cell metabolism and cancer metabolism has grown significantly in the past decade, we are on the cusp of being able to unravel the interaction of cancer cell metabolism and immune metabolism in therapeutically meaningful ways. Although there are metabolic processes that are seemingly fundamental to both cancer and responding immune cells, metabolic heterogeneity and plasticity may serve to distinguish the two. As such, understanding the differential metabolic requirements of the diverse cells that comprise an immune response to cancer offers an opportunity to selectively regulate immune cell function. Such a nuanced evaluation of cancer and immune metabolism can uncover metabolic vulnerabilities and therapeutic windows upon which to intervene for enhanced immunotherapy.
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