英国伦敦大学玛丽皇后学院Daniel J. Pennington团队发现，肿瘤微环境中的γδT细胞亚群具有独特的代谢程序。该研究于2021年1月18日在线发表于国际一流学术期刊《自然—免疫学》。

研究人员发现，产生干扰素-γ（IFN-γ）或白介素（IL）-17的γδT细胞亚群具有本质上不同的代谢需求。IFN-γ⁺γδT细胞几乎完全依赖糖酵解，而IL-17⁺γδT细胞强烈参与氧化代谢，从而增加了线粒体的质量和活性。这些独特的代谢特征令人惊讶地在胸腺发育早期被印刻，并稳定地维持在肿瘤的周围和内部。而且，促肿瘤的IL-17⁺γδT细胞选择性地显示高脂质摄取和细胞内脂质存储，并且在肥胖症和肥胖小鼠的肿瘤中扩增。

相反，补充过氧化物时，葡萄糖补充可增强IFN-γ⁺γδT细胞的抗肿瘤功能，并减少肿瘤的生长。这些发现对效应子γδT细胞的分化及其在癌症免疫治疗中的操作具有重要意义。

据介绍，代谢程序控制免疫细胞谱系和功能，但对γδT细胞代谢了解甚少。

附：英文原文

Title: Distinct metabolic programs established in the thymus control effector functions of γδ T cell subsets in tumor microenvironments

Author: Noella Lopes, Claire McIntyre, Stefania Martin, Mathilde Raverdeau, Nital Sumaria, Ayano C. Kohlgruber, Gina J. Fiala, Leandro Z. Agudelo, Lydia Dyck, Harry Kane, Aaron Douglas, Stephen Cunningham, Hannah Prendeville, Roisin Loftus, Colleen Carmody, Philippe Pierre, Manolis Kellis, Michael Brenner, Rafael J. Argello, Bruno Silva-Santos, Daniel J. Pennington, Lydia Lynch

Issue&Volume: 2021-01-18

Abstract: Metabolic programming controls immune cell lineages and functions, but little is known about γδ T cell metabolism. Here, we found that γδ T cell subsets making either interferon-γ (IFN-γ) or interleukin (IL)-17 have intrinsically distinct metabolic requirements. Whereas IFN-γ+ γδ T cells were almost exclusively dependent on glycolysis, IL-17+ γδ T cells strongly engaged oxidative metabolism, with increased mitochondrial mass and activity. These distinct metabolic signatures were surprisingly imprinted early during thymic development and were stably maintained in the periphery and within tumors. Moreover, pro-tumoral IL-17+ γδ T cells selectively showed high lipid uptake and intracellular lipid storage and were expanded in obesity and in tumors of obese mice. Conversely, glucose supplementation enhanced the antitumor functions of IFN-γ+ γδ T cells and reduced tumor growth upon adoptive transfer. These findings have important implications for the differentiation of effector γδ T cells and their manipulation in cancer immunotherapy.

DOI: 10.1038/s41590-020-00848-3

Source: https://www.nature.com/articles/s41590-020-00848-3