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Interferon Gamma Secretion of Adaptive and Innate Immune Cells as a Parameter to Describe Leukaemia-Derived Dendritic-Cell-Mediated Immune Responses in Acute Myeloid Leukaemia in vitro.
- Source :
-
Transfusion Medicine & Hemotherapy . 2022, Vol. 49 Issue 1, p44-61. 18p. - Publication Year :
- 2022
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Abstract
- Introduction: Myeloid leukaemic blasts can be converted into leukaemia-derived dendritic cells (DCleu), characterised by the simultaneous expression of dendritic- and leukaemia-associated antigens, which have the competence to prime and enhance (leukaemia-specific) immune responses with the whole leukaemic antigen repertoire. To display and further specify dendritic cell (DC)- and DCleu-mediated immune responses, we analysed the interferon gamma (IFNy) secretion of innate and adaptive immune cells. Methods: DC/DCleu were generated from leukaemic whole blood (WB) with (blast)modulatory Kit-I (granulocyte-macrophage colony-stimulating factor [GM-CSF] + Picibanil [OK-432]) and Kit-M (GM-CSF + prostaglandin E1) and were used to stimulate T cell-enriched immunoreactive cells. Initiated anti-leukaemic cytotoxicity was investigated with a cytotoxicity fluorolysis assay. Initiated IFNy secretion of T, NK, CIK, and iNKT cells was investigated with a cytokine secretion assay (CSA). IFNy positivity was additionally evaluated with an intracellular cytokine assay (ICA). Recent activation of leukaemia-specific cells was verified through addition of leukaemia-associated antigens (LAA; WT-1 and Prame) Results: We found Kit-I and Kit-M competent to generate mature DC and DCleu from leukaemic WB without induction of blast proliferation. Stimulation of immunoreactive cells with DC/DCleu regularly resulted in an increased anti-leukaemic cytotoxicity and increased IFNy secretion of T, NK, and CIK cells, pointing to the significant role of DC/DCleu in leukaemia-specific alongside anti-leukaemic reactions. Interestingly, an addition of LAA did not further increase IFNy secretion, suggesting an efficient activation of leukaemia-specific cells. Here, both the CSA and ICA yielded comparable frequencies of IFNy-positive cells. Remarkably, the anti-leukaemic cytotoxicity positively correlated with the IFNy secretion in TCD3+, TCD4+, TCD8+, and NKCD56+ cells. Conclusion: Ultimately, the IFNy secretion of innate and adaptive immune cells appeared to be a suitable parameter to assess and monitor the efficacy of in vitro and potentially in vivo acute myeloid leukaemia immunotherapy. The CSA in this regard proved to be a convenient and reproducible technique to detect and phenotypically characterise IFNy-secreting cells. In respect to our studies on DC-based immunomodulation, we were able to display the potential of DC/DCleu to induce or improve leukaemia-specific and anti-leukaemic activity. [ABSTRACT FROM AUTHOR]
- Subjects :
- *ACUTE myeloid leukemia
*INTERFERON gamma
*GRANULOCYTE-macrophage colony-stimulating factor
*IMMUNE response
*PROSTAGLANDIN E1
*DENDRITIC cells
*IN vitro studies
*FLOW cytometry
*CYTOKINES
*ACADEMIC medical centers
*INTERFERONS
*PEARSON correlation (Statistics)
*T-test (Statistics)
*IMMUNITY
*CELL proliferation
*STATISTICAL hypothesis testing
*DESCRIPTIVE statistics
*T cells
*CELL surface antigens
*IMMUNODIAGNOSIS
Subjects
Details
- Language :
- English
- ISSN :
- 16603796
- Volume :
- 49
- Issue :
- 1
- Database :
- Academic Search Index
- Journal :
- Transfusion Medicine & Hemotherapy
- Publication Type :
- Academic Journal
- Accession number :
- 155051272
- Full Text :
- https://doi.org/10.1159/000516886