近日，美国匹兹堡大学教授Greg M. Delgoffe及其团队报道了肿瘤间质液富集的磷酸乙醇胺抑制T细胞功能。2025年4月21日出版的《自然—细胞生物学》杂志发表了这项成果。

因此，该课题组研究人员设计了一种基于肿瘤间质液代谢组学特征的化学定义细胞培养基：肿瘤间质液培养基（TIFM）。在TIFM中培养CD8⁺ T细胞限制了细胞的扩增，并在再刺激时损害了CD8⁺ T细胞的效应功能，这表明肿瘤的营养应激本身就足以驱动T细胞功能障碍。该课题组发现磷酸乙醇胺（pEtn），一种磷脂中间体，作为T细胞功能障碍的驱动因素。pEtn通过消耗T细胞受体信号转导所需的二酰基甘油来抑制T细胞受体信号转导。肿瘤中pEtn积累的减少改善了瘤内T细胞功能和肿瘤控制，表明pEtn积累在肿瘤微环境的免疫抑制中起主导作用。

研究人员表示，营养应激是抗肿瘤免疫的重要屏障，而肿瘤间质液通常含有阻碍免疫功能的代谢物。然而，很难将肿瘤营养应激的影响从其他抑制因素中分离出来。

附：英文原文

Title: Tumour interstitial fluid-enriched phosphoethanolamine suppresses T cell function

Author: Wang, Yupeng, Wilfahrt, Drew, Jonker, Patrick, Lontos, Konstantinos, Cai, Chufan, Cameron, Benjamin, Xie, Bingxian, Peralta, Ronal M., Schoedel, Emerson R., Gunn, William G., AminiTabrizi, Roya, Shah, Hardik, Rivadeneira, Dayana B., Muir, Alexander, Delgoffe, Greg M.

Issue&Volume: 2025-04-21

Abstract: Nutrient stress represents an important barrier for anti-tumour immunity, and tumour interstitial fluid often contains metabolites that hinder immune function. However, it is difficult to isolate the effects of tumour nutrient stress from other suppressive factors. Thus, we used a chemically defined cell culture medium based on the metabolomic profile of tumour interstitial fluid: tumour interstitial fluid medium (TIFM). Culture of CD8+ T cells in TIFM limited cell expansion and impaired CD8+ T cell effector functions upon restimulation, suggesting that tumour nutrient stress alone is sufficient to drive T cell dysfunction. We identified phosphoethanolamine (pEtn), a phospholipid intermediate, as a driver of T cell dysfunction. pEtn dampened T cell receptor signalling by depleting T cells of diacylglycerol required for T cell receptor signal transduction. The reduction of pEtn accumulation in tumours improved intratumoural T cell function and tumour control, suggesting that pEtn accumulation plays a dominant role in immunosuppression in the tumour microenvironment.

DOI: 10.1038/s41556-025-01650-9

Source: https://www.nature.com/articles/s41556-025-01650-9