γδ T-cell Receptors Derived from Breast Cancer-Infiltrating T Lymphocytes Mediate Antitumor Reactivity.

Autor:	Janssen A; Laboratory of Translational Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands., Villacorta Hidalgo J; Institute for Surgical Pathology, University Medical Center, University of Freiburg, Freiburg, Germany.; Faculty of Biology, University of Freiburg, Freiburg, Germany.; Faculty of Medicine, University of Freiburg, Freiburg, Germany., Beringer DX; Laboratory of Translational Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands., van Dooremalen S; Laboratory of Translational Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands., Fernando F; Laboratory of Translational Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands., van Diest E; Laboratory of Translational Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands., Terrizi AR; Institute for Surgical Pathology, University Medical Center, University of Freiburg, Freiburg, Germany.; Faculty of Medicine, University of Freiburg, Freiburg, Germany., Bronsert P; Institute for Surgical Pathology, University Medical Center, University of Freiburg, Freiburg, Germany.; Faculty of Medicine, University of Freiburg, Freiburg, Germany.; German Cancer Consortium (DKTK) and Cancer Research Center (DKFZ), Heidelberg, Germany.; Comprehensive Cancer Center Freiburg, Medical Center - University of Freiburg, Freiburg, Germany., Kock S; Institute for Surgical Pathology, University Medical Center, University of Freiburg, Freiburg, Germany.; Faculty of Medicine, University of Freiburg, Freiburg, Germany., Schmitt-Gräff A; Institute for Surgical Pathology, University Medical Center, University of Freiburg, Freiburg, Germany.; Faculty of Medicine, University of Freiburg, Freiburg, Germany., Werner M; Institute for Surgical Pathology, University Medical Center, University of Freiburg, Freiburg, Germany.; Faculty of Medicine, University of Freiburg, Freiburg, Germany.; German Cancer Consortium (DKTK) and Cancer Research Center (DKFZ), Heidelberg, Germany.; Comprehensive Cancer Center Freiburg, Medical Center - University of Freiburg, Freiburg, Germany., Heise K; Institute of Cell Biology (Cancer Research), University of Duisburg-Essen, Essen, Germany., Follo M; Faculty of Medicine, University of Freiburg, Freiburg, Germany.; Department of Medicine I, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany., Straetemans T; Laboratory of Translational Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands., Sebestyen Z; Laboratory of Translational Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands., Chudakov DM; Privolzhsky Research Medical University, Nizhny Novgorod, Russia.; Center for Data-Intensive Biomedicine and Biotechnology, Skolkovo Institute of Science and Technology, Moscow, Russia.; Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Moscow, Russia., Kasatskaya SA; Center for Data-Intensive Biomedicine and Biotechnology, Skolkovo Institute of Science and Technology, Moscow, Russia.; Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Moscow, Russia., Frenkel FE; BostonGene LLC, Lincoln, Nebraska., Ravens S; Institute of Immunology, Hannover Medical School, Hannover, Germany., Spierings E; Laboratory of Translational Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands., Prinz I; Institute of Immunology, Hannover Medical School, Hannover, Germany., Küppers R; Institute of Cell Biology (Cancer Research), University of Duisburg-Essen, Essen, Germany., Malkovsky M; UW School of Medicine and Public Health, Madison, Wisconsin., Fisch P; Institute for Surgical Pathology, University Medical Center, University of Freiburg, Freiburg, Germany.; Faculty of Medicine, University of Freiburg, Freiburg, Germany., Kuball J; Laboratory of Translational Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands. j.h.e.kuball@umcutrecht.nl.; Department of Hematology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands.
Jazyk:	angličtina
Zdroj:	Cancer immunology research [Cancer Immunol Res] 2020 Apr; Vol. 8 (4), pp. 530-543. Date of Electronic Publication: 2020 Feb 04.
DOI:	10.1158/2326-6066.CIR-19-0513
Abstrakt:	γδ T cells in human solid tumors remain poorly defined. Here, we describe molecular and functional analyses of T-cell receptors (TCR) from tumor-infiltrating γδ T lymphocytes (γδ TIL) that were in direct contact with tumor cells in breast cancer lesions from archival material. We observed that the majority of γδ TILs harbored a proinflammatory phenotype and only a minority associated with the expression of IL17. We characterized TCRγ or TCRδ chains of γδ TILs and observed a higher proportion of Vδ2 + T cells compared with other tumor types. By reconstructing matched Vδ2 - TCRγ and TCRδ pairs derived from single-cell sequencing, our data suggest that γδ TILs could be active against breast cancer and other tumor types. The reactivity pattern against tumor cells depended on both the TCRγ and TCRδ chains and was independent of additional costimulation through other innate immune receptors. We conclude that γδ TILs can mediate tumor reactivity through their individual γδ TCR pairs and that engineered T cells expressing TCRγ and δ chains derived from γδ TILs display potent antitumor reactivity against different cancer cell types and, thus, may be a valuable tool for engineering immune cells for adoptive cell therapies. (©2020 American Association for Cancer Research.)
Databáze:	MEDLINE
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