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

Standard

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 journalSCORING: Journal articleResearchpeer-review

Harvard

Janssen, A, Villacorta Hidalgo, J, Beringer, DX, van Dooremalen, S, Fernando, F, van Diest, E, Terrizi, AR, Bronsert, P, Kock, S, Schmitt-Gräff, A, Werner, M, Heise, K, Follo, M, Straetemans, T, Sebestyen, Z, Chudakov, DM, Kasatskaya, SA, Frenkel, FE, Ravens, S, Spierings, E, Prinz, I, Küppers, R, Malkovsky, M, Fisch, P & Kuball, J 2020, 'γδ T-cell Receptors Derived from Breast Cancer-Infiltrating T Lymphocytes Mediate Antitumor Reactivity', CANCER IMMUNOL RES, vol. 8, no. 4, pp. 530-543. https://doi.org/10.1158/2326-6066.CIR-19-0513

APA

Janssen, A., Villacorta Hidalgo, J., Beringer, D. X., van Dooremalen, S., Fernando, F., van Diest, E., Terrizi, A. R., Bronsert, P., Kock, S., Schmitt-Gräff, A., Werner, M., Heise, K., Follo, M., Straetemans, T., Sebestyen, Z., Chudakov, D. M., Kasatskaya, S. A., Frenkel, F. E., Ravens, S., ... Kuball, J. (2020). γδ T-cell Receptors Derived from Breast Cancer-Infiltrating T Lymphocytes Mediate Antitumor Reactivity. CANCER IMMUNOL RES, 8(4), 530-543. https://doi.org/10.1158/2326-6066.CIR-19-0513

Vancouver

Janssen A, Villacorta Hidalgo J, Beringer DX, van Dooremalen S, Fernando F, van Diest E et al. γδ T-cell Receptors Derived from Breast Cancer-Infiltrating T Lymphocytes Mediate Antitumor Reactivity. CANCER IMMUNOL RES. 2020 Apr;8(4):530-543. https://doi.org/10.1158/2326-6066.CIR-19-0513

Bibtex

@article{95fb18addaab46c397121af77793d812,
title = "γδ T-cell Receptors Derived from Breast Cancer-Infiltrating T Lymphocytes Mediate Antitumor Reactivity",
abstract = "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.",
keywords = "Adult, Aged, Aged, 80 and over, Case-Control Studies, Cell Line, Tumor, Coculture Techniques, Female, Healthy Volunteers, High-Throughput Nucleotide Sequencing/methods, Humans, Immunotherapy, Adoptive/methods, Leukocytes, Mononuclear/immunology, Lymphocytes, Tumor-Infiltrating/immunology, Middle Aged, Receptors, Antigen, T-Cell, gamma-delta/genetics, T-Lymphocyte Subsets/immunology, Triple Negative Breast Neoplasms/genetics",
author = "Anke Janssen and {Villacorta Hidalgo}, Jose and Beringer, {Dennis X} and {van Dooremalen}, Sanne and Febilla Fernando and {van Diest}, Eline and Terrizi, {Antonela R} and Peter Bronsert and Sylvia Kock and Annette Schmitt-Gr{\"a}ff and Martin Werner and Kerstin Heise and Marie Follo and Trudy Straetemans and Zsolt Sebestyen and Chudakov, {Dmitry M} and Kasatskaya, {Sofya A} and Frenkel, {Felix E} and Sarina Ravens and Eric Spierings and Immo Prinz and Ralf K{\"u}ppers and Miroslav Malkovsky and Paul Fisch and J{\"u}rgen Kuball",
note = "{\textcopyright}2020 American Association for Cancer Research.",
year = "2020",
month = apr,
doi = "10.1158/2326-6066.CIR-19-0513",
language = "English",
volume = "8",
pages = "530--543",
journal = "CANCER IMMUNOL RES",
issn = "2326-6066",
publisher = "American Association for Cancer Research Inc.",
number = "4",

}

RIS

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 -