Chemotherapy pretreatment sensitizes solid tumor-derived cell lines to Vα24+ NKT cell-mediated cytotoxicity

Mattarollo, Stephen R., Kenna, Tony, Nieda, Mie, & Nicol, Andrew J. (2006) Chemotherapy pretreatment sensitizes solid tumor-derived cell lines to Vα24+ NKT cell-mediated cytotoxicity. International Journal of Cancer, 119(7), pp. 1630-1637.

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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.

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ID Code: 94067
Item Type: Journal Article
Refereed: Yes
Keywords: Antitumor, Cancer, Chemotherapy, Immunotherapy, NKT cells, antineoplastic agent, cisplatin, death receptor 5, doxorubicin, etoposide, Fas antigen, FAS ligand, natural killer cell receptor, natural killer cell receptor Valpha24, natural killer cell receptor Vbeta11, tumor necrosis factor related apoptosis inducing ligand, unclassified drug, antineoplastic activity, article, cancer cell culture, cancer chemotherapy, controlled study, cytotoxicity, human, human cell, immunoregulation, natural killer T cell, priority journal, prostate cancer, solid tumor, Antineoplastic Agents, Apoptosis Regulatory Proteins, Cell Line, Tumor, Cell Survival, Cytotoxicity, Immunologic, Fas Ligand Protein, Humans, Membrane Glycoproteins, Neoplasms, Receptors, Antigen, T-Cell, Receptors, Tumor Necrosis Factor, T-Lymphocytes, Regulatory, TNF-Related Apoptosis-Inducing Ligand, Tumor Necrosis Factor-alpha, Tumor Necrosis Factors, Up-Regulation
DOI: 10.1002/ijc.22019
ISSN: 0020-7136
Divisions: Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
Copyright Owner: Copyright 2006 Wiley-Liss, Inc.
Deposited On: 22 Mar 2016 05:38
Last Modified: 23 Mar 2016 04:26

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