Role of EVs as promotors for activation of leukemia-derived dendritic cell (DCleu)-mediated antileukemic immune response against AML-blasts

Abstract

Abstract Myeloid leukemia blasts can be converted into dendritic cells of leukemic origin (DCleu), which effectively activate and enhance immune-cells against leukemic blasts. EVs modulate a plethora of physiological and pathological activities. EVs secreted by dendritic cells (DCs) can activate T lymphocytes, displaying potential as promoters of adaptive immune responses. DC/DCleu generation of healthy donors’ (n=9) and AML patients’ (n=9) whole blood (WB) were treated with Kit M (GM-CSF and PGE1) (vs. control), T-cell enriched mixed lymphocyte culture (MLC) with treated vs un-treated WB and antileukemic functional assays were quantified via flow cytometry. Qualitative and quantitative characterization EVs from DC/MLC culture supernatants (DCS/MLCS) in healthy and AML samples were measured. Kit M significantly increased frequencies of (mature) DC/DCleu compared to control without induction of blast proliferation. Kit M increased significantly activated (leukemia-specific) cells of the adaptive and innate immune system after T cell-enriched MLC compared to control. EVs were qualitatively and quantitatively different in DCS/MLCS with Kit M treated vs untreated from healthy vs AML samples by TEM, fNTA and MBFCM. These EVs findings and correlations with clinical parameters contribute to understand the functional role of EVs in DCS/MLCS from healthy and AML samples, with respect to develop new EV biomarkers.