2026-02-26 カリフォルニア大学ロサンゼルス校（UCLA）
＜関連情報＞
- https://newsroom.ucla.edu/releases/ucla-researchers-discover-how-to-supercharge-immune-cells-tumors-cancer
- https://www.cell.com/cell/abstract/S0092-8674(26)00102-9
真菌由来のセロビオース代謝経路はT細胞に腫瘍内グルコース競合を回避するよう働きかける Fungal-derived cellobiose metabolic pathway fuels T cells to bypass intratumoral glucose competition
Matthew L. Miller ∙ Timothy J. Thauland ∙ Smriti Sameer Nagarajan ∙ Wenqi Ellen Zuo ∙ Miguel A. Moreno Lastre ∙ Manish J. Butte
Cell Published:February 24, 2026
DOI:https://doi.org/10.1016/j.cell.2026.01.015
Graphical abstract
Highlights
- Two fungal genes added to T cells allow cellobiose (glucose polysaccharide) metabolism
- Cellobiose restores glycolysis and metabolite pools despite glucose withdrawal
- Fueling with cellobiose rescues T-cell survival, proliferation, and cytokines
- Cellobiose-metabolizing T cells exhibit superior tumor control in vivo
Summary
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.
