Interleukin-15 enhances the proliferation, stimulatory phenotype, and antitumor effector functions of human gamma delta T cells. Issue 1 (December 2016)

• Record Type: Journal Article
• Authors: Van Acker, Heleen; Anguille, Sébastien; Willemen, Yannick; Van den Bergh, Johan; Berneman, Zwi; Lion, Eva; Smits, Evelien; Van Tendeloo, Viggo
• Is Part Of: Journal of hematology & oncology. Volume 9:Issue 1(2016)
• Page Start: 1
• Page End: 13
• Publication Date: 2016-12
• Subjects: Adoptive transfer -- Expansion protocol -- Gamma delta T cells -- Interleukin-15 -- Leukemia; Hematology -- Periodicals; Oncology -- Periodicals; Blood -- Diseases -- Periodicals; 616.994
• DOI: 10.1186/s13045-016-0329-3
• Languages: English
• ISSNs: 1756-8722

Abstract

Abstract 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.