1. Dendritic/antigen presenting cell mediated provision of T-cell receptor gamma delta (TCRγδ) expressing cells contributes to improving antileukemic reactions ex vivo.
- Author
-
Rackl E, Hartz A, Aslan Rejeski H, Li L, Klauer LK, Ugur S, Pepeldjiyska E, Amend C, Weinmann M, Doraneh-Gard F, Stein J, Reiter N, Seidel CL, Plett C, Amberger DC, Bojko P, Kraemer D, Schmohl J, Rank A, Schmid C, and Schmetzer HM
- 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 (DC
leu )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., Competing Interests: Declaration of Competing Interest H.M.S. is involved with Modiblast Pharma GmbH (Oberhaching, Germany), holder of the European Patent 15 801 987.7–1118 and the US Patent 15–517627 “Use of immunomodulatory effective compositions for the immunotherapeutic treatment of patients suffering from myeloid leukemias”., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)- Published
- 2024
- Full Text
- View/download PDF