TY - JOUR
T1 - γδ T-cell Receptors Derived from Breast Cancer-Infiltrating T Lymphocytes Mediate Antitumor Reactivity
AU - Janssen, Anke
AU - Villacorta Hidalgo, Jose
AU - Beringer, Dennis X.
AU - van Dooremalen, Sanne
AU - Fernando, Febilla
AU - van Diest, Eline
AU - Terrizi, Antonela R.
AU - Bronsert, Peter
AU - Kock, Sylvia
AU - Schmitt-Gräff, Annette
AU - Werner, Martin
AU - Heise, Kerstin
AU - Follo, Marie
AU - Straetemans, Trudy
AU - Sebestyen, Zsolt
AU - Chudakov, Dmitry M.
AU - Kasatskaya, Sofya A.
AU - Frenkel, Felix E.
AU - Ravens, Sarina
AU - Spierings, Eric
AU - Prinz, Immo
AU - Küppers, Ralf
AU - Malkovsky, Miroslav
AU - Fisch, Paul
AU - Kuball, J. rgen
N1 - Funding Information: Funding for this study was provided by ZonMW 43400003 and VIDI-ZonMW 917.11.337, KWF UU 2010-4669, UU 2013-6426, UU 2014-6790 and UU 2015-7601, UU 2018-11393, Vrienden van het UMCU, AICR 10-0736 and 15-0049, and Gadeta to J. Kuball, Lady Tata Memorial Trust and UU 2018-11393 to Z. Sebestyen, and SFB1160 Z2 to P. Fisch. J. Villacorta Hidalgo was supported by a PhD scholarship from Deutscher Akademischer Austauschdienst (DAAD). D.M. Chudakov is supported by grant of the Ministry of Education and Science of the Russian Federation (no. 14.W03.31.0005). We are grateful to Nagesha Appukudige for supporting computational analyses; Guido Kierkels for critical Publisher Copyright: © 2020 American Association for Cancer Research Inc.. All rights reserved. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2020/4/1
Y1 - 2020/4/1
N2 - 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 gd TILs and observed a higher proportion of Vδ +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 TCRg 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 TCRpairs 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.
AB - 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 gd TILs and observed a higher proportion of Vδ +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 TCRg 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 TCRpairs 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.
UR - http://www.scopus.com/inward/record.url?scp=85082979236&partnerID=8YFLogxK
U2 - https://doi.org/10.1158/2326-6066.CIR-19-0513
DO - https://doi.org/10.1158/2326-6066.CIR-19-0513
M3 - Article
C2 - 32019779
SN - 2326-6066
VL - 8
SP - 530
EP - 543
JO - Cancer immunology research
JF - Cancer immunology research
IS - 4
ER -