title: Analysis of Immune Cells from Human Mammary Ductal Epithelial Organoids Reveals Vδ2+ T Cells That Efficiently Target Breast Carcinoma Cells in the Presence of Bisphosphonate.
abstract: Developing strategies to enhance cancer prevention is a paramount goal, particularly given recent concerns about surgical treatment of preinvasive states such as ductal carcinoma in situ. Promoting effective immunosurveillance by leukocytes that scan for nascent neoplastic transformations represents a potential means to achieve this goal. Because most breast cancers arise within the ductal epithelium, enhancing protective immunosurveillance will likely necessitate targeting one or more of the distinctive lymphocyte types found in these sites under normal conditions. Here, we have characterized the intraepithelial lymphocyte compartment of non-cancerous human breast tissue and identified a subset of T lymphocytes that can be pharmacologically targeted to enhance their responses to breast cancer cells. Specifically, Vδ2(+) γδ T cells were consistently present in preparations of mammary ductal epithelial organoids and they proliferated in response to zoledronic acid, an aminobisphosphonate drug. Vδ2(+) T cells from breast ductal organoids produced the antitumor cytokine IFNγ and efficiently killed bisphosphonate-pulsed breast carcinoma cells. These findings demonstrate the potential for exploiting the ability of Vδ2(+) γδ T cells to respond to FDA-approved bisphosphonate drugs as a novel immunotherapeutic approach to inhibit the outgrowth of breast cancers.
authors.affiliation: Department of Medical Microbiology and Immunology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin. McArdle Laboratory for Cancer Research, Department of Oncology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin.
authors.forename: Nicholas A
authors.initials: NA
authors.lastname: Zumwalde
authors.affiliation: McArdle Laboratory for Cancer Research, Department of Oncology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin.
authors.forename: Jill D
authors.initials: JD
authors.lastname: Haag
authors.affiliation: McArdle Laboratory for Cancer Research, Department of Oncology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin.
authors.forename: Deepak
authors.initials: D
authors.lastname: Sharma
authors.affiliation: Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin.
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Mirrielees
authors.affiliation: Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin.
authors.forename: Lee G
authors.initials: LG
authors.lastname: Wilke
authors.affiliation: McArdle Laboratory for Cancer Research, Department of Oncology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin. jegumperz@wisc.edu gould@oncology.wisc.edu.
authors.forename: Michael N
authors.initials: MN
authors.lastname: Gould
authors.affiliation: Department of Medical Microbiology and Immunology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin. jegumperz@wisc.edu gould@oncology.wisc.edu.
authors.forename: Jenny E
authors.initials: JE
authors.lastname: Gumperz
mesh_terms: D002285:Carcinoma, Intraductal, Noninfiltrating / Q000276:immunology* / Q000517:prevention & control; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic; D004164:Diphosphonates / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D007157:Immunologic Surveillance / Q000187:drug effects; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism*; D042361:Mammary Glands, Human / Q000166:cytology* / Q000276:immunology; D009940:Organoids / Q000166:cytology*; D061251:Primary Cell Culture; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D000077211:Zoledronic Acid
chemical_list: D004164:Diphosphonates; C573415:IFNG protein, human; D007093:Imidazoles; D000077211:Zoledronic Acid; D007371:Interferon-gamma
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