Interleukin-15 enhances the proliferation, stimulatory phenotype, and antitumor effector functions of human gamma delta T cells
| Autor: | Yannick Willemen, Zwi N. Berneman, Eva Lion, Heleen H. Van Acker, Johan M.J. Van den Bergh, Viggo Van Tendeloo, Evelien Smits, Sébastien Anguille |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Cancer Research T cell Biology Gamma delta T cells lcsh:RC254-282 03 medical and health sciences Interleukin 21 0302 clinical medicine medicine Cytotoxic T cell IL-2 receptor Antigen-presenting cell Molecular Biology Interleukin 3 Interleukin-15 Leukemia lcsh:RC633-647.5 Research ZAP70 Adoptive transfer Hematology lcsh:Diseases of the blood and blood-forming organs Natural killer T cell lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens 030104 developmental biology medicine.anatomical_structure Oncology Expansion protocol Immunology Human medicine 030215 immunology |
| Zdroj: | Journal of Hematology & Oncology, Vol 9, Iss 1, Pp 1-13 (2016) Journal of Hematology & Oncology Journal of hematology and oncology |
| ISSN: | 1756-8722 |
| DOI: | 10.1186/s13045-016-0329-3 |
| Popis: | Background Adoptive immunotherapy is gaining momentum to fight malignancies, whereby γδ T cells have received recent attention as an alternative cell source as to natural killer cells and αβ T cells. The advent of γδ T cells is largely due to their ability to recognize and target tumor cells using both innate characteristic and T cell receptor (TCR)-mediated mechanisms, their capacity to enhance the generation of antigen-specific T cell responses, and their potential to be used in an autologous or allogeneic setting. Methods In this study, we explored the beneficial effect of the immunostimulatory cytokine interleukin (IL)-15 on purified γδ T cells and its use as a stimulatory signal in the ex vivo expansion of γδ T cells for adoptive transfer. The expansion protocol was validated both with immune cells of healthy individuals and acute myeloid leukemia patients. Results We report that the addition of IL-15 to γδ T cell cultures results in a more activated phenotype, a higher proliferative capacity, a more pronounced T helper 1 polarization, and an increased cytotoxic capacity of γδ T cells. Moreover γδ T cell expansion starting with peripheral blood mononuclear cells from healthy individuals and acute myeloid leukemia patients is boosted in the presence of IL-15, whereby the antitumor properties of the γδ T cells are strengthened as well. Conclusions Our results support the rationale to explore the use of IL-15 in clinical adoptive therapy protocols exploiting γδ T cells. |
| Databáze: | OpenAIRE |
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