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Enhancing tumor-infiltrating T cells with an exclusive fuel source. | LitMetric

AI Article Synopsis

  • - Solid tumors create an immunosuppressive environment that weakens tumor-infiltrating lymphocytes (TILs) by consuming glucose, which hampers their function.
  • - Researchers explored the use of cellobiose, a glucose disaccharide that tumors can't break down, to provide TILs with a new energy source, enhancing their activity when glucose is scarce.
  • - Supplementing T cells with cellobiose proteins not only restores their ability to produce cytokines and proliferate but also leads to reduced tumor growth and extended survival in mice, indicating a potential new method for enhancing cancer immunotherapy and studying glucose metabolism in various biological contexts.

Article 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 a building block of cellulose, contains a β-1,4-glycosidic bond that cannot be hydrolyzed by animals (or their tumors), but fungal and bacterial organisms have evolved enzymes to catabolize cellobiose and use the resulting glucose. By equipping T cells with two proteins that enable import and hydrolysis of cellobiose, we demonstrate that supplementation of cellobiose during glucose withdrawal restores T cell cytokine production and cellular proliferation. Murine tumor growth is suppressed and survival is prolonged. Offering exclusive access to a natural disaccharide is a new tool that augments cancer immunotherapies. Beyond cancer, this approach could be used to answer questions about the regulation of glucose metabolism across many cell types, biological processes, and diseases.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11142041PMC
http://dx.doi.org/10.1101/2024.05.20.595053DOI Listing

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