Expression of ligands of the activating receptor NKG2D in pre-malignant (myelodysplastic syndrome) and malignant (leukemia) blasts and lymphoid cells

SECCHIARI, FLORENCIA; NÚÑEZ, SOL YANEL; TORRES, NICOLÁS IGNACIO; SIERRA, JESSICA MARIEL; ZIBLAT, ANDREA; FUERTES, MERCEDES BEATRIZ; DOMAICA, CAROLINA INÉS; ZWIRNER, NORBERTO WALTER

Mar del Plata

Congreso; 64a Reunión Anual de la Sociedad Argentina de Inmunología; 2016

Sociedad Argentina de Inmunología

Different tumors express a diverse array of ligands ofthe NK cell activating receptor NKG2D. These molecules comprise MICA, MICB and6 members of the ULBP family (ULBP1 to 6) and are generically known as NKG2Dligands (NKG2DLs). However, the pattern and relevance of the differentialand/or combined expression of these NKG2DLs remains unknown in many cases.Nonetheless, as these molecules may constitute attractive targets forimmunotherapy and potential prognostic and/or therapeutic biomarkers, athorough characterization of the expression pattern of NKG2DLs or ?NKG2DLoma? may reveal interesting informationassociated with disease status, progression, response to therapy and otherclinical parameters. Therefore, the aim of this study was to initiate thecharacterization of the NKG2DLomaexpressed by peripheral blood mononuclear cells (PBMCs) from patients with leukemia(with focus on acute myelogenous leukemia) and myelodysplastic syndrome (MDS),as well as from healthy donors using multicolor flow cytometry. For leukemiapatients (n=6), variable degrees of expression of MICA, MICB, ULBP2,5,6, ULBP3and/or ULBP4 were observed on blasts and, unexpectedly, on lymphoid cells; whilefor MDS samples (n=5) only MICB and/or ULBP4 expression was observed on blasts (andin a few cases also on lymphoid cells). Conversely, very low levels of NKG2DLswere observed on lymphoid cells from healthy donors (n=6), while higherexpression of MICA, ULBP2,5,6 and ULBP3 were expressed by lymphoid cells fromleukemia samples (p<0.05 for all of them). Our results suggest that a morerestricted array of NKG2DLs is expressed during pre-malignancy stages onblasts; while such array of NKG2DLs broadens as the disease progresses towardsmalignancy and also extends from blasts to lymphoid cells.