Dendritic/antigen presenting cell mediated provision of T-cell receptor gamma delta (TCRγδ) expressing cells contributes to improving antileukemic reactions ex vivo

Rackl, Elias; Hartz, Anne; Aslan Rejeski, Hazal; Li, Lin; Klauer, Lara Kristina; Ugur, Selda; Pepeldjiyska, Elena; Amend, Carina; Weinmann, Melanie; Doraneh-Gard, Fatemeh; Stein, Julian; Reiter, Nina; Seidel, Corinna L.; Plett, Caroline; Amberger, Daniel Christoph; Bojko, Peter; Kraemer, Doris; Schmohl, Jörg; Rank, Andreas; Schmid, Christoph und Schmetzer, Helga Maria (2024): Dendritic/antigen presenting cell mediated provision of T-cell receptor gamma delta (TCRγδ) expressing cells contributes to improving antileukemic reactions ex vivo. In: Molecular Immunology, Bd. 175: S. 40-54

Abstract

T-cell receptor gamma delta (TCRγδ) expressing T-cells are known to mediate an MHC-independent immune response and could therefore qualify for immune therapies. We examined the influence of dendritic cells(DC)/antigen presenting cell (APC) generated from blast-containing whole blood (WB) samples from AML and MDS patients on the provision of (leukemia-specific) TCRγδ expressing T-cells after mixed lymphocyte culture (MLC). Kit-M (granulocyte-macrophage colony-stimulating factor (GM-CSF) + prostaglandin E1 (PGE1)) or Kit-I (GM-CSF + Picibanil) were used to generate leukemia derived APC/DC (DCleu)from WB, which were subsequently used to stimulate T-cell enriched MLC. Immune cell composition and functionality were analysed using degranulation- (DEG), intracellular cytokine- (INTCYT) and cytotoxicity fluorolysis- (CTX) assays. Flow cytometry was used for cell quantification. We found increased frequencies of APCs/DCs and their subtypes after Kit-treatment of healthy and patients´ WB compared to control, as well as an increased stimulation and activation of several types of immune reactive cells after MLC. Higher frequencies of TCRγδ expressing leukemia-specific degranulation and intracellularly cytokine producing T-cells were found. The effect of Kit-M-treatment on frequencies of TCRγδ expressing cells and their degranulation could be correlated with the Kit-M-mediated blast lysis compared to control. We also found higher frequencies of TCRγδ expressing T-cells in AML patients´ samples with an achieved remission (compared to blast persistence) after induction chemotherapy. This might point to APC/DC-mediated effects resulting in the provision of leukemia-specific TCRγδ expressing T-cells: Moreover a quantification of TCRγδ expressing T-cells might contribute to predict prognosis of AML/MDS patients.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin > Klinikum der LMU München > Medizinische Klinik und Poliklinik III (Onkologie)
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 01615890
• Sprache: Englisch