In:
Transfusion Medicine and Hemotherapy, S. Karger AG, Vol. 49, No. 1 ( 2022), p. 44-61
Abstract:
〈 b 〉 〈 i 〉 Introduction: 〈 /i 〉 〈 /b 〉 Myeloid leukaemic blasts can be converted into leukaemia-derived dendritic cells (DC 〈 sub 〉 leu 〈 /sub 〉 ), 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 DC 〈 sub 〉 leu 〈 /sub 〉 -mediated immune responses, we analysed the interferon gamma (IFNy) secretion of innate and adaptive immune cells. 〈 b 〉 〈 i 〉 Methods: 〈 /i 〉 〈 /b 〉 DC/DC 〈 sub 〉 leu 〈 /sub 〉 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) 〈 b 〉 〈 i 〉 Results: 〈 /i 〉 〈 /b 〉 We found Kit-I and Kit-M competent to generate mature DC and DC 〈 sub 〉 leu 〈 /sub 〉 from leukaemic WB without induction of blast proliferation. Stimulation of immunoreactive cells with DC/DC 〈 sub 〉 leu 〈 /sub 〉 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/DC 〈 sub 〉 leu 〈 /sub 〉 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 T 〈 sup 〉 CD3+ 〈 /sup 〉 , T 〈 sup 〉 CD4+ 〈 /sup 〉 , T 〈 sup 〉 CD8+ 〈 /sup 〉 , and NK 〈 sup 〉 CD56+ 〈 /sup 〉 cells. 〈 b 〉 〈 i 〉 Conclusion: 〈 /i 〉 〈 /b 〉 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/DC 〈 sub 〉 leu 〈 /sub 〉 to induce or improve leukaemia-specific and anti-leukaemic activity.
Type of Medium:
Online Resource
ISSN:
1660-3796
,
1660-3818
Language:
English
Publisher:
S. Karger AG
Publication Date:
2022
detail.hit.zdb_id:
2100533-3
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