{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T22:41:39Z","timestamp":1778625699337,"version":"3.51.4"},"reference-count":12,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","license":[{"start":{"date-parts":[[2021,7,1]],"date-time":"2021-07-01T00:00:00Z","timestamp":1625097600000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Immunometabolism"],"abstract":"<jats:sec>\n            <jats:title>Abstract<\/jats:title>\n            <jats:p>Solid tumour targeting using adoptive cell therapy has failed to reproduce the spectacular clinical successes seen with chimeric antigen receptor T cell therapies and B cell malignancies. Low in glucose, oxygen, pH and populated with suppressive cells, the solid tumour microenvironment (TME) remains a formidable obstacle to successful immune targeting. The use of atypical, tissue-tropic lymphocytes, such as \u03b3\u03b4T cells, may offer enhanced tumour trafficking over canonical \u03b1\u03b2T cells. Nonetheless, \u03b3\u03b4T cells too interact with the TME. The consequences of this interaction are poorly understood and of high translational relevance. Lopes and colleagues sho w that, in a murine context, low glucose environments preferentially retained pro-tumorigenic IL-17-producing \u03b3\u03b4T cells. Anti-tumorigenic IFN-\u03b3-producing \u03b3\u03b4T cells, meanwhile, required high ambient glucose to survive and exert effector function. Unexpectedly, this metabolic imprinting was evident in the murine thymus, suggesting that the ontological separation of these functional subsets occurs early in their development. Elucidation of this relationship between TME glucose levels and \u03b3\u03b4T cell functionality in a human context is likely to carry significant implications for the development of \u03b3\u03b4T cell-based oncoimmunotherapeutics.<\/jats:p>\n          <\/jats:sec>","DOI":"10.20900\/immunometab20210026","type":"journal-article","created":{"date-parts":[[2021,7,30]],"date-time":"2021-07-30T07:57:35Z","timestamp":1627631855000},"update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":4,"title":["Interplay between \u03b3\u03b4T-Cell Metabolism and Tumour Microenvironment Offers Opportunities for Therapeutic Intervention"],"prefix":"10.1097","volume":"3","author":[{"given":"Marta","family":"Barisa","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel","family":"Fowler","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jonathan","family":"Fisher","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","published-online":{"date-parts":[[2021,7]]},"reference":[{"key":"ref0","doi-asserted-by":"publisher","unstructured":"1. Maude SL, Frey N, Shaw PA, Aplenc R, Barrett DM, Bunin NJ, et al. Chimeric Antigen Receptor T Cells for Sustained Remissions in Leukemia, N Engl J Med. 2014 Oct 16;371(16):1507-17.","DOI":"10.1056\/NEJMoa1407222"},{"key":"ref1","doi-asserted-by":"publisher","first-page":"1341","DOI":"10.1038\/s41591-019-0564-6","article-title":"Clinical lessons learned from the first leg of the CAR T cell journey","volume":"25","author":"RG","year":"2019","unstructured":"2. Majzner RG, Mackall CL. Clinical lessons learned from the first leg of the CAR T cell journey. Nat Med. 2019;25:1341-55.","journal-title":"Nat Med"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"128","DOI":"10.3389\/fimmu.2019.00128","article-title":"CAR T Cells for Solid Tumors: New Strategies for Finding, Infiltrating, and Surviving in the Tumor Microenvironment","volume":"10","author":"Martinez","year":"2019","unstructured":"3. Martinez M, Moon EK. CAR T Cells for Solid Tumors: New Strategies for Finding, Infiltrating, and Surviving in the Tumor Microenvironment. Front Immunol. 2019;10:128.","journal-title":"Front Immunol"},{"key":"ref3","doi-asserted-by":"publisher","unstructured":"4. Yu W-L, Hua Z-C. Chimeric Antigen Receptor T-cell (CAR T) Therapy for Hematologic and Solid Malignancies: Efficacy and Safety-A Systematic Review with Meta-Analysis. Cancers. 2019 Jan 7;11(1):47.","DOI":"10.3390\/cancers11010047"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"938","DOI":"10.1038\/nm.3909","article-title":"The prognostic landscape of genes and infiltrating immune cells across human cancers","volume":"21","author":"Gentles","year":"2015","unstructured":"5. Gentles AJ, Newman AM, Liu CL, Bratman SV, Feng W, Kim D, et al. The prognostic landscape of genes and infiltrating immune cells across human cancers. Nat Med. 2015;21:938-945.","journal-title":"Nat Med"},{"key":"ref5","doi-asserted-by":"publisher","unstructured":"6. 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Cell Mol Immunol. 2021;18:427-39.","journal-title":"Cell Mol Immunol"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"570","DOI":"10.1016\/j.cell.2017.04.004","article-title":"Metabolic Instruction of Immunity","volume":"169","author":"Buck","year":"2017","unstructured":"8. Buck MD, Sowell RT, Kaech SM, Pearce EL. Metabolic Instruction of Immunity. Cell. 2017;169:570-86.","journal-title":"Cell"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"461","DOI":"10.1146\/annurev-immunol-042617-053019","article-title":"Unraveling the Complex Interplay Between T Cell Metabolism and Function","volume":"36","author":"Geltink","year":"2018","unstructured":"9. Geltink RIK, Kyle RL, Pearce EL. Unraveling the Complex Interplay Between T Cell Metabolism and Function. 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