γδ T cell dichotomy with opposing cytotoxic and wound healing functions in human solid tumors.

Autor: Harmon C; Department of Endocrinology, Brigham & Women's Hospital, Boston, MA, USA.; Department of Medicine, Harvard Medical School, Boston, MA, USA., Zaborowski A; School of Biochemistry and Immunology, Trinity College Dublin, Dublin, Ireland.; Centre for Colorectal Disease, St. Vincent's University Hospital, Dublin, Ireland., Moore H; Department of Medicine, Harvard Medical School, Boston, MA, USA., St Louis P; Program in Molecular Medicine and the Diabetes Center of Excellence, University of Massachusetts Chan Medical School, Worcester, MA, USA., Slattery K; School of Biochemistry and Immunology, Trinity College Dublin, Dublin, Ireland., Duquette D; Department of Endocrinology, Brigham & Women's Hospital, Boston, MA, USA.; Department of Medicine, Harvard Medical School, Boston, MA, USA.; School of Biochemistry and Immunology, Trinity College Dublin, Dublin, Ireland., Scanlan J; Department of Endocrinology, Brigham & Women's Hospital, Boston, MA, USA.; Department of Medicine, Harvard Medical School, Boston, MA, USA.; School of Biochemistry and Immunology, Trinity College Dublin, Dublin, Ireland., Kane H; Department of Endocrinology, Brigham & Women's Hospital, Boston, MA, USA.; Department of Medicine, Harvard Medical School, Boston, MA, USA.; School of Biochemistry and Immunology, Trinity College Dublin, Dublin, Ireland., Kunkemoeller B; Department of Endocrinology, Brigham & Women's Hospital, Boston, MA, USA.; Department of Medicine, Harvard Medical School, Boston, MA, USA., McIntyre CL; Department of Endocrinology, Brigham & Women's Hospital, Boston, MA, USA.; Department of Medicine, Harvard Medical School, Boston, MA, USA., Scannail AN; Department of Endocrinology, Brigham & Women's Hospital, Boston, MA, USA.; Department of Medicine, Harvard Medical School, Boston, MA, USA., Moran B; Department of Pathology, St. Vincent's University Hospital, Dublin, Ireland., Anderson AC; Evergrande Center for Immunologic Diseases and Ann Romney Center for Neurologic Diseases, Harvard Medical School and Brigham & Women's Hospital, Boston, MA, USA., Winter D; Centre for Colorectal Disease, St. Vincent's University Hospital, Dublin, Ireland., Brennan D; Gynecological Oncology Group, School of Medicine, University College Dublin, Dublin, Ireland., Brehm MA; Program in Molecular Medicine and the Diabetes Center of Excellence, University of Massachusetts Chan Medical School, Worcester, MA, USA., Lynch L; Department of Endocrinology, Brigham & Women's Hospital, Boston, MA, USA. llynch@bwh.harvard.edu.; Department of Medicine, Harvard Medical School, Boston, MA, USA. llynch@bwh.harvard.edu.; School of Biochemistry and Immunology, Trinity College Dublin, Dublin, Ireland. llynch@bwh.harvard.edu.
Jazyk: angličtina
Zdroj: Nature cancer [Nat Cancer] 2023 Aug; Vol. 4 (8), pp. 1122-1137. Date of Electronic Publication: 2023 Jul 20.
DOI: 10.1038/s43018-023-00589-w
Abstrakt: γδ T cells are important tissue-resident, innate T cells that are critical for tissue homeostasis. γδ cells are associated with positive prognosis in most tumors; however, little is known about their heterogeneity in human cancers. Here, we phenotyped innate and adaptive cells in human colorectal (CRC) and endometrial cancer. We found striking differences in γδ subsets and function in tumors compared to normal tissue, and in the γδ subsets present in tumor types. In CRC, an amphiregulin (AREG)-producing subset emerges, while endometrial cancer is infiltrated by cytotoxic cells. In humanized CRC models, tumors induced this AREG phenotype in Vδ1 cells after adoptive transfer. To exploit the beneficial roles of γδ cells for cell therapy, we developed an expansion method that enhanced cytotoxic function and boosted metabolic flexibility, while eliminating AREG production, achieving greater tumor infiltration and tumor clearance. This method has broad applications in cellular therapy as an 'off-the-shelf' treatment option.
(© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.)
Databáze: MEDLINE
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