Fungal-derived cellobiose metabolic pathway fuels T cells to bypass intratumoral glucose competition
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 equi
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# Fungal-derived cellobiose metabolic pathway fuels T cells to bypass intratumoral glucose competition
*Published: 2026 Mar 19*
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