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

Anke Janssen, José Villacorta Hidalgo, Dennis X Beringer, Sanne F.J. van Dooremalen, Febilla Fernando, Eline van Diest, Antonela R Terrizzi, Peter Bronsert, Sylvia Kock, Annette Schmitt-Graeff, Martin Werner, Kerstin Heise, Marie Follo, Trudy Straetemans, Zsolt Sebestyen, Dmitriy M Chudakov, Sofya A Kasatskaya, Felix E Frenkel, Sarina Ravens, Eric SpieringsImmo Prinz, Ralf Küppers, Miroslav Malkovsky, Paul Fisch, Jurgen Kuball

Research output: Contribution to journalArticleAcademicpeer-review


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.

Original languageEnglish
Pages (from-to)530-543
Number of pages14
JournalCancer Immunology Research
Issue number4
Early online date4 Feb 2020
Publication statusPublished - Apr 2020


  • 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


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