TY - JOUR TI - Distinct metabolic programs established in the thymus control effector functions of γδ T cell subsets in tumor microenvironments AU - Lopes, Noella AU - McIntyre, Claire AU - Martin, Stefania AU - Raverdeau, Mathilde AU - Sumaria, Nital AU - Kohlgruber, Ayano C. AU - Fiala, Gina J. AU - Agudelo, Leandro Z. AU - Dyck, Lydia AU - Kane, Harry AU - Douglas, Aaron AU - Cunningham, Stephen AU - Prendeville, Hannah AU - Loftus, Roisin AU - Carmody, Colleen AU - Pierre, Philippe AU - Kellis, Manolis AU - Brenner, Michael AU - Argüello, Rafael J. AU - Silva-Santos, Bruno AU - Pennington, Daniel J. AU - Lynch, Lydia T2 - Nature Immunology AB - Metabolic programming controls immune cell lineages and functions, but little is known about γδ T cell metabolism. Here, we found that γδ T cell subsets making either interferon-γ (IFN-γ) or interleukin (IL)-17 have intrinsically distinct metabolic requirements. Whereas IFN-γ+ γδ T cells were almost exclusively dependent on glycolysis, IL-17+ γδ T cells strongly engaged oxidative metabolism, with increased mitochondrial mass and activity. These distinct metabolic signatures were surprisingly imprinted early during thymic development and were stably maintained in the periphery and within tumors. Moreover, pro-tumoral IL-17+ γδ T cells selectively showed high lipid uptake and intracellular lipid storage and were expanded in obesity and in tumors of obese mice. Conversely, glucose supplementation enhanced the antitumor functions of IFN-γ+ γδ T cells and reduced tumor growth upon adoptive transfer. These findings have important implications for the differentiation of effector γδ T cells and their manipulation in cancer immunotherapy. DA - 2021/01/18/ PY - 2021 DO - 10.1038/s41590-020-00848-3 DP - www.nature.com SP - 1 EP - 14 LA - en SN - 1529-2916 UR - https://www.nature.com/articles/s41590-020-00848-3 Y2 - 2021/01/19/00:10:03 ER -