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γδ T-cell Receptors Derived from Breast Cancer-Infiltrating T Lymphocytes Mediate Antitumor Reactivity.
- Source :
-
Cancer immunology research [Cancer Immunol Res] 2020 Apr; Vol. 8 (4), pp. 530-543. Date of Electronic Publication: 2020 Feb 04. - Publication Year :
- 2020
-
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 <superscript>+</superscript> T cells compared with other tumor types. By reconstructing matched Vδ2 <superscript>-</superscript> 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.<br /> (©2020 American Association for Cancer Research.)
- Subjects :
- Adult
Aged
Aged, 80 and over
Case-Control Studies
Cell Line, Tumor
Coculture Techniques
Female
Healthy Volunteers
High-Throughput Nucleotide Sequencing methods
Humans
Middle Aged
Receptors, Antigen, T-Cell, gamma-delta genetics
Triple Negative Breast Neoplasms genetics
Triple Negative Breast Neoplasms pathology
Triple Negative Breast Neoplasms therapy
Immunotherapy, Adoptive methods
Leukocytes, Mononuclear immunology
Lymphocytes, Tumor-Infiltrating immunology
Receptors, Antigen, T-Cell, gamma-delta immunology
T-Lymphocyte Subsets immunology
Triple Negative Breast Neoplasms immunology
Subjects
Details
- Language :
- English
- ISSN :
- 2326-6074
- Volume :
- 8
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Cancer immunology research
- Publication Type :
- Academic Journal
- Accession number :
- 32019779
- Full Text :
- https://doi.org/10.1158/2326-6066.CIR-19-0513