真菌来源的纤维素糖代谢途径为T细胞提供燃料，以绕过肿瘤内的葡萄糖竞争，这一成果由加州大学Manish J. Butte课题组经过不懈努力而取得。相关论文于2026年2月24日发表在《细胞》杂志上。

小组试图通过为TIL提供完全的燃料供应来恢复其功能。葡萄糖二糖纤维素二糖是纤维素的组成部分，它含有一种动物（或它们的肿瘤）无法水解的β-1,4-糖苷键，但真菌和微生物已经进化出酶来分解纤维素二糖，使其成为有糖的葡萄糖。研究小组在小鼠T细胞和人类嵌合抗原受体(CAR)-T细胞中植入两种来自真菌的蛋白，这两种蛋白能够导入和水解纤维素二糖，研究小组证明了在葡萄糖停药期间补充纤维素二糖可以恢复关键的抗肿瘤T细胞功能：活力、增殖、细胞因子产生和细胞毒性杀伤。提供纤维素二糖的工程化T细胞抑制肿瘤生长并延长生存期。提供独特的途径，以一种天然双糖增强癌症免疫治疗。这种方法可以回答关于许多细胞类型、生物过程和疾病的葡萄糖代谢问题。

据介绍，实体肿瘤含有免疫抑制微环境，通过大量消耗葡萄糖来抑制肿瘤浸润淋巴细胞（TILs）。

附：英文原文

Title: Fungal-derived cellobiose metabolic pathway fuels T cells to bypass intratumoral glucose competition

Author: Matthew L. Miller, Timothy J. Thauland, Smriti Sameer Nagarajan, Wenqi Ellen Zuo, Miguel A. Moreno Lastre, Manish J. Butte

Issue&Volume: 2026-02-24

Abstract: Solid tumors harbor immunosuppressive microenvironments that inhibit tumor-infiltrating lymphocytes (TILs) through the voracious consumption of glucose. We sought to restore TIL function by providing them with an exclusive fuel source. The glucose disaccharide cellobiose, which is the building block of cellulose, contains a β-1,4-glycosidic bond that animals (or their tumors) cannot hydrolyze, but fungi and microbes have evolved enzymes to catabolize cellobiose into useful glucose. We equipped mouse T cells and human chimeric antigen receptor (CAR)-T cells with two proteins derived from fungi that enable import and hydrolysis of cellobiose, and we demonstrated that cellobiose supplementation during glucose withdrawal restores key anti-tumor T-cell functions: viability, proliferation, cytokine production, and cytotoxic killing. Engineered T cells offered cellobiose suppress tumor growth and prolong survival. Offering exclusive access to a natural disaccharide augments cancer immunotherapies. This approach could be used to answer questions about glucose metabolism across many cell types, biological processes, and diseases.

DOI: 10.1016/j.cell.2026.01.015

Source: https://www.cell.com/cell/abstract/S0092-8674(26)00102-9