Journal article
Comparison of γδ T cell responses and farnesyl diphosphate synthase inhibition in tumor cells pretreated with zoledronic acid
Cancer science, Vol.104(5), pp.536-542
05/2013
DOI: 10.1111/cas.12124
PMCID: PMC3755363
PMID: 23387443
Abstract
Exposing human tumor cells to nitrogen‐containing bisphosphonates, such as zoledronic acid (Zol), greatly increases their susceptibility to killing by γδ T cells. Based on this finding and other studies, cancer immunotherapy using γδ T cells and nitrogen‐containing bisphosphonates has been studied in pilot clinical trials and has shown benefits. Although Zol treatment can render a wide variety of human tumor cells susceptible to γδ T cell killing, there has not been a systematic investigation to determine which types of tumor cells are the most susceptible to γδ T cell‐mediated cytotoxicity. In this study, we determined the Zol concentrations required to stimulate half maximal tumor necrosis factor‐α production by γδ T cells cultured with various tumor cell lines pretreated with Zol and compared these concentrations with those required for half maximal inhibition of farnesyl diphosphate synthase (
FPPS
) in the same tumor cell lines. The inhibition of tumor cell growth by Zol was also assessed. We found that
FPPS
inhibition strongly correlated with γδ T cell activation, confirming that the mechanism underlying γδ T cell activation by Zol is isopentenyl diphosphate (IPP) accumulation due to
FPPS
blockade. In addition, we showed that γδ T‐cell receptor‐mediated signaling correlated with γδ T cell tumor necrosis factor‐α production and cytotoxicity. Some lymphoma, myeloid leukemia, and mammary carcinoma cell lines were relatively resistant to Zol treatment, suggesting that assessing tumor sensitivity to Zol may help select those patients most likely to benefit from immunotherapy with γδ T cells.
Details
- Title: Subtitle
- Comparison of γδ T cell responses and farnesyl diphosphate synthase inhibition in tumor cells pretreated with zoledronic acid
- Creators
- Atif S. M Idrees - Kyoto UniversityTomoharu Sugie - Kyoto UniversityChiyomi Inoue - Kyoto UniversityKaoru Murata‐Hirai - Kyoto UniversityHaruki Okamura - Hyogo College of MedicineCraig T Morita - University of Iowa Carver College of MedicineNagahiro Minato - Graduate School of MedicineMasakazu Toi - Kyoto UniversityYoshimasa Tanaka - Kyoto University
- Resource Type
- Journal article
- Publication Details
- Cancer science, Vol.104(5), pp.536-542
- Publisher
- John Wiley and Sons Inc
- DOI
- 10.1111/cas.12124
- PMID
- 23387443
- PMCID
- PMC3755363
- ISSN
- 1347-9032
- eISSN
- 1349-7006
- Grant note
- Scientific Research from the Ministry of Education, Science, Culture, Sports, and Technology of Japan (MEXT) Veterans Health Administration CA113874; CA097274‐11 / National Institutes of Health Department of Veterans Affairs 1BX000972 / Biomedical Laboratory Research and Development AR045504 / National Institutes of Health National Institute of Arthritis and Musculoskeletal and Skin Disease National Cancer Institute Office of Research and Development
- Alternative title
- Idrees et al
- Language
- English
- Date published
- 05/2013
- Academic Unit
- Immunology; Internal Medicine
- Record Identifier
- 9984094575002771
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