Chemotherapy pretreatment sensitizes solid tumor-derived cell lines to V alpha 24(+) NKT cell-mediated cytotoxicity

Mattarollo, Stephen R., Kenna, Tony, Niedal, Mie and Nicol, Andrew J. (2006) Chemotherapy pretreatment sensitizes solid tumor-derived cell lines to V alpha 24(+) NKT cell-mediated cytotoxicity. International Journal of Cancer, 119 7: 1630-1637. doi:10.1002/ijc.22019

Author Mattarollo, Stephen R.
Kenna, Tony
Niedal, Mie
Nicol, Andrew J.
Title Chemotherapy pretreatment sensitizes solid tumor-derived cell lines to V alpha 24(+) NKT cell-mediated cytotoxicity
Formatted title
Chemotherapy pretreatment sensitizes solid tumor-derived cell lines to Vα24+ NKT cell-mediated cytotoxicity
Journal name International Journal of Cancer   Check publisher's open access policy
ISSN 0020-7136
Publication date 2006-10-01
Sub-type Article (original research)
DOI 10.1002/ijc.22019
Volume 119
Issue 7
Start page 1630
End page 1637
Total pages 8
Place of publication New York, USA
Publisher John Wiley & Sons, Inc.
Collection year 2006
Language eng
Subject C1
730108 Cancer and related disorders
320202 Cellular Immunology
110707 Innate Immunity
110709 Tumour Immunology
1107 Immunology
1112 Oncology and Carcinogenesis
Formatted abstract
There is an increasing awareness of the therapeutic potential for combining immune-based therapies with chemotherapy in the treatment of malignant diseases, but few published studies evaluate possible cytotoxic synergies between chemotherapy and cytotoxic immune cells. Human Vα24+/Vβ11+ NKT cells are being evaluated for use in cell-based immunotherapy of malignancy because of their immune regulatory functions and potent cytotoxic potential. In this study, we evaluated the cytotoxicity of combinations of chemotherapy and NKT cells to determine whether there is a potential to combine these treatment modalities for human cancer therapy. The cytotoxicity of NKT cells was tested against solid-tumor derived cell lines NCI-H358, DLD-1, HT-29, DU-145, TSU-Pr1 and MDA-MB231, with or without prior treatment of these target cells, with a range of chemotherapy agents. Low concentrations of chemotherapeutic agents led to sensitization of cell lines to NKT-mediated cytotoxicity, with the greatest effect being observed for prostate cancer cells. Synergistic cytotoxicity occurred in an NKT cell in a dose-dependent manner. Chemotherapy agents induced upregulation of cell surface TRAIL-R2 (DR5) and Fas (CD95) expression, increasing the capacity for NKT cells to recognize and kill via TRAIL- and FasL-mediated pathways. We conclude that administration of cytotoxic immune cells after chemotherapy may increase antitumor activities in comparison with the use of either treatment alone. © 2006 Wiley-Liss, Inc.
Keyword Oncology
Nkt Cells
Alpha-galactosylceramide Krn7000
Trail-induced apoptosis
Antitumor immunity
Dendritic cells
Q-Index Code C1

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
2007 Higher Education Research Data Collection
School of Medicine Publications
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Citation counts: TR Web of Science Citation Count  Cited 22 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 25 times in Scopus Article | Citations
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Created: Wed, 15 Aug 2007, 09:57:34 EST