Bloomberg~Kimmel Institute for Cancer Immunotherapy, Sidney Kimmel Comprehensive Cancer Research Center, Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Nat Rev Cancer. 2020 Sep;20(9):516-531. doi: 10.1038/s41568-020-0273-y. Epub 2020 Jul 6.
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.
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一种既定治疗方法。细胞代谢已成为癌症细胞和免疫细胞存活和功能的关键决定因素。为了维持巨大的合成代谢需求，肿瘤采用了一种不同于未转化体细胞的特殊代谢方式。这种代谢导致肿瘤微环境通常呈酸性、缺氧和/或缺乏免疫细胞所需的关键营养物质。在这种情况下，肿瘤代谢本身就是一个检查点，可以限制免疫介导的肿瘤破坏。由于我们在过去十年中对免疫细胞代谢和癌症代谢的理解有了显著的提高，我们即将能够以有治疗意义的方式揭示癌细胞代谢和免疫代谢的相互作用。尽管有一些代谢过程似乎对癌症和反应性免疫细胞都是基本的，但代谢异质性和可塑性可能有助于区分两者。因此，了解构成对癌症免疫反应的不同细胞的差异代谢需求，为选择性调节免疫细胞功能提供了机会。对癌症和免疫代谢的这种细致评估，可以揭示代谢脆弱性和治疗窗口，从而增强免疫治疗效果。
