γδ T-cell Receptors Derived from Breast Cancer-Infiltrating T Lymphocytes Mediate Antitumor Reactivity
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γδ T-cell Receptors Derived from Breast Cancer-Infiltrating T Lymphocytes Mediate Antitumor Reactivity. / Janssen, Anke; Villacorta Hidalgo, Jose; Beringer, Dennis X; van Dooremalen, Sanne; Fernando, Febilla; van Diest, Eline; Terrizi, Antonela R; Bronsert, Peter; Kock, Sylvia; Schmitt-Gräff, Annette; Werner, Martin; Heise, Kerstin; Follo, Marie; Straetemans, Trudy; Sebestyen, Zsolt; Chudakov, Dmitry M; Kasatskaya, Sofya A; Frenkel, Felix E; Ravens, Sarina; Spierings, Eric; Prinz, Immo; Küppers, Ralf; Malkovsky, Miroslav; Fisch, Paul; Kuball, Jürgen.
In: CANCER IMMUNOL RES, Vol. 8, No. 4, 04.2020, p. 530-543.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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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, Jürgen
N1 - ©2020 American Association for Cancer Research.
PY - 2020/4
Y1 - 2020/4
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 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.
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 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.
KW - Adult
KW - Aged
KW - Aged, 80 and over
KW - Case-Control Studies
KW - Cell Line, Tumor
KW - Coculture Techniques
KW - Female
KW - Healthy Volunteers
KW - High-Throughput Nucleotide Sequencing/methods
KW - Humans
KW - Immunotherapy, Adoptive/methods
KW - Leukocytes, Mononuclear/immunology
KW - Lymphocytes, Tumor-Infiltrating/immunology
KW - Middle Aged
KW - Receptors, Antigen, T-Cell, gamma-delta/genetics
KW - T-Lymphocyte Subsets/immunology
KW - Triple Negative Breast Neoplasms/genetics
U2 - 10.1158/2326-6066.CIR-19-0513
DO - 10.1158/2326-6066.CIR-19-0513
M3 - SCORING: Journal article
C2 - 32019779
VL - 8
SP - 530
EP - 543
JO - CANCER IMMUNOL RES
JF - CANCER IMMUNOL RES
SN - 2326-6066
IS - 4
ER -