Ex vivo expanded human Vgamma9Vdelta2+ gammadelta-T cells mediate innate antitumor activity against human prostate cancer cells in vitro.
PURPOSE: We have previously identified a CD2 mediated, interleukin-12 dependent signaling pathway that inhibits activation induced cell death in mitogen stimulated human gammadelta-T cells, permitting the large-scale expansion of these cells. Herein we report the innate antitumor activity of expanded human Vgamma9Vdelta2+ gammadelta-T cells against human prostate cancer cells. MATERIALS AND METHODS: Apoptosis resistant human gammadelta-T cells were expanded in vitro from cultured human peripheral blood mononuclear cells and then enriched to high purity by immunomagnetic separation. In vitro cytotoxicity of expanded gammadelta-T cells was measured against human prostate cancer cell lines using standard cytotoxicity assays. RESULTS: gammadelta-T cells derived from various donors consistently showed lytic activity against the prostate cancer cell lines DU-145 and PC-3 but not LNCaP. mAbs against Vgamma9 or Vdelta2 T-cell receptor chains as well as mAb against intercellular adhesion molecule-1 (ICAM-1) or CD18, the beta subunit of ICAM-1 counter receptors, blocked gammadelta-T cell mediated killing of prostate cancer cells. gammadelta-T cells lysed prostate cancer cell lines largely through the perforin/granzyme pathway. CONCLUSIONS: Ex vivo, expanded human Vgamma9Vdelta2+ gammadelta-T cells are able innately to recognize and kill certain human prostate tumor cell lines in vitro. The recognition and killing of prostate cancer cells occurs in a gammadelta-T-cell receptor dependent manner and it also appears to involve interactions between ICAM-1 and CD18. Because apoptosis resistant human Vgamma9Vdelta2+ gammadelta-T cells can readily be expanded to large numbers (clinical scale), these findings must be considered in the context of developing adoptive immunotherapy strategies to exploit gammadelta-T cell innate immune responses to prostate cancer.
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Related Subject Headings
- Urology & Nephrology
- Tumor Cells, Cultured
- T-Lymphocytes
- Receptors, Antigen, T-Cell, gamma-delta
- Prostatic Neoplasms
- Male
- Humans
- Drug Screening Assays, Antitumor
- 3202 Clinical sciences
- 1103 Clinical Sciences
Citation
Published In
DOI
ISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Urology & Nephrology
- Tumor Cells, Cultured
- T-Lymphocytes
- Receptors, Antigen, T-Cell, gamma-delta
- Prostatic Neoplasms
- Male
- Humans
- Drug Screening Assays, Antitumor
- 3202 Clinical sciences
- 1103 Clinical Sciences