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将 T 细胞代谢纳入癌症免疫治疗。

Integrating T cell metabolism in cancer immunotherapy.

机构信息

Beta Cell Biology Unit, Diabetes Research Institute, IRCCS San Raffaele Scientific Institute, Via Olgettina 60, Milan, Italy.

Transplant Immunology Unit, Diabetes Research Institute, IRCCS San Raffaele Scientific Institute, Via Olgettina 60, Milan, Italy.

出版信息

Cancer Lett. 2017 Dec 28;411:12-18. doi: 10.1016/j.canlet.2017.09.039. Epub 2017 Sep 30.

Abstract

Activation and maintenance of the T cell response occurs concurrently with metabolic reprogramming. This ensures the T cell response is supported by sufficient energy and substrates necessary for cell survival, growth and proliferation. Different metabolic programs are associated with differentiation into different cell subsets, effector function and development of long-lasting memory. This provides an opportunity to improve the T cell response through manipulation of metabolism, which is instrumental to ameliorate the current protocols for cancer immunotherapy. Using drugs and molecules targeting selective metabolic pathways it is now possible to generate T cells that can mount a durable and stable anti-tumor response. On the other hand, cancer cells can take advantage of the metabolic requirements of T cells to evade the immune response. In this brief review we discuss recent findings of T cell metabolism in quiescence and activation, how the tumor microenvironment can affect T cell metabolism, and how T cell metabolism can be manipulated to improve the T cell response to tumors.

摘要

T 细胞反应的激活和维持伴随着代谢重编程。这确保了 T 细胞反应得到足够的能量和细胞存活、生长和增殖所需的底物的支持。不同的代谢程序与分化为不同的细胞亚群、效应功能和产生持久记忆有关。这为通过代谢操纵来改善 T 细胞反应提供了机会,这对于改善癌症免疫治疗的当前方案至关重要。使用靶向选择性代谢途径的药物和分子,现在可以产生能够产生持久和稳定的抗肿瘤反应的 T 细胞。另一方面,癌细胞可以利用 T 细胞的代谢需求来逃避免疫反应。在这篇简要综述中,我们讨论了静止和激活的 T 细胞代谢的最新发现,肿瘤微环境如何影响 T 细胞代谢,以及如何操纵 T 细胞代谢来提高 T 细胞对肿瘤的反应。

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