Background Antileukemic responses of immune reactive cells in AML-patients need to be improved. Combinations of blast-modulatory kitM (GM-CSF+PGE1) (vs control) convert myeloid blasts into dendritic cells of leukemic origin (DCleu), that effectively activate immune-cells against leukemic blasts. DC-derived EVs express molecules and carry nucleic acids (eg. miRNA) with immune regulatory functions.
Materials and Methods 1) DC/DCleu-generation of blast containing AML patients‘ (n=5) and of healthy volunteers(n=5) whole blood (WB) with kit M; 2) T-cell enriched mixed lymphocyte culture (MLC) with kit- vs un-treated WB; 3) antileukemic functional assays; 4) Sequencing of EV-derived miRNA from culture supernatants; 5) Qualitative/quantitative characterization of (leukemia/healthy) supernatant derived EVs and EV derived miRNAs as biomarkers.
Results 1) kitM increased significantly frequencies of (mature) DC/DCleu compared to untreated WB without induction of blasts’ proliferation. 2) kitM treated vs untreated WB increased significantly activated (leukemia-specific) cells of the adaptive and innate immune system after T cell-enriched MLC. 3a) EVs were qualitatively and quantitatively different in DC/MLC culture supernatants compared control as well as 3b) in kitM treated vs untreated healthy and AML samples. 3c) Different EV derived miRNAs were up- or downregulated in DC/MLC culture supernatants.
Conclusions These findings contribute to understand the unique/functional role of (leukemic derived) DCs to improve antileukemic immune responses, with respect to the role of EVs/EV derived miRNA and to potentially deduce new EV derived biomarkers.
Disclosure Information L. Li: None. V. Mussack: None. A. Görgens: None. E. Pepeldjiyska: None. A.S. Hartz: None. H. Aslan: None. E. Rackl: None. A. Rank: None. J. Schmohl: None. M.W. Pfaffl: None. H. Schmetzer: None.
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