1459 Association with stemness and functional role of immunoreceptor NKG2D expression in acute myeloid leukemia

• DOI: 10.1136/jitc-2023-sitc2023.1459
• Publication Date: 2023-10-31T14:58:29Z
• Authors: Ilona Hagelstein; Sylwia A Stefanczyk; Kim L Clar; Kathrin Rothfelder; Jonas Rieth; Jonas S Heitmann; Helmut R Salih
• Keywords: NKG2D; CTL*

<h3>Background</h3> The activating immunoreceptor NKG2D is expressed on cytotoxic lymphocytes (CTL) like NK cells, CD8⁺ T cells and γδ cells. It potently stimulates CTL effector functions upon recognition of its ligands (NKG2DL) that are generally absent healthy tissue, but induced by cellular stress including malignant transformation. Recent studies demonstrated – somewhat surprisingly - also the receptor can be tumor various origins may affect growth metastasis. Here we report role expression in acute myeloid leukemia (AML). <h3>Methods</h3> Expression cell surface patient AML correlation with differentiation/maturation as well stemness characteristics depending were studied. Furthermore, functional signaling stem properties was investigated. <h3>Results</h3> Primary leukemic patients substantial levels approximately 40% 156 investigated patients. Within cohort, associated more differentiated subtypes according to FAB classification. Notably, within population individual patients, significantly correlated CD34 negativity. In line, after sorting bulk expression, only subpopulation lacking showed ability give rise colonies colony forming unit assays. Exposure NKG2D-positive agonistic antibody caused release cytokines IL-6, IL-8, IL-10 TNF, which act survival factors for play an important disease pathophysiology. stimulation further increased engraftment primary NSG mice. Signaling via found enhance metabolic activity/viability protected from treatment cytostatic compounds cytarabine doxorubicin routinely used treatment. <h3>Conclusions</h3> Taken together, our data implicate NKG2D/NKG2DL system, beyond involvement immune surveillance, directly Ongoing investigations aim unravel NKG2D-mediated pathways, consequences autocrine/paracrine interaction association negativity known stemness/differentiation markers clinical course. <h3>Ethics Approval</h3> study approved IRB (ethics committee Faculty Medicine Eberhard Karls Universitaet Tuebingen University Hospital Tuebingen) conducted accordance Declaration Helsinki; reference number 13/2007V. <h3>Consent</h3> Human material collected obtaining written informed consent patients/participants.