Leukemia derived dendritic cell (DCleu) mediated immune response goes along with reduced (leukemia-specific) regulatory T-cells |
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| Affiliation: | 1. WG Immune Modulation, Medical Department III, University Hospital of Munich, Marchioninistraße 15, 81377 Munich, Germany;2. Department of Orthodontics and Orofacial Orthopedics, Universitätsklinikum Erlangen and Friedrich-Alexander Universität (FAU) Erlangen-Nürnberg, Glückstr. 11, 91054 Erlangen, Germany;3. Diakonie Hospital Stuttgart, Department Hematology and Oncology, Department of Internal Medicine, Rosenbergstraße 38, 70176 Stuttgart, Germany;4. Department of Haematology, Oncology and Palliative Care, Kath. Krankenhaus Hagen gem. GmbH, St.-Josefs-Hospital, Dreieckstraße 17, 58097 Hagen, Germany;5. Department of Haematology and Oncology, University Hospital of Augsburg, Stenglinstraße 2, 86156 Augsburg, Germany;1. Department of Biotechnology, SRM Institute of Science and Technology, Kattankulathur, Tamil Nadu 603203, India;2. Department of Clinical Pharmacology, SRM Medical College Hospital and Research Centre, Kattankulathur, Tamil Nadu 603203, India;1. Programa de Pós-Graduação em Patologia Ambiental e Experimental, Universidade Paulista (UNIP), Rua Dr. Bacelar 902, CEP 04057-000, São Paulo, SP, Brazil;2. Faculdade de Medicina da Universidade Federal de Alagoas, Campus A. C. Simões Tabuleiro do Martins, CEP 57072-900, Maceió, AL, Brazil;3. Departamento de Fisiopatologia, Instituto Butantan, Av. Vital Brasil 1500, CEP 05503-900, São Paulo, SP, Brazil;4. Pesquisadora associada, Pós-Doutoranda da Companhia Ambiental do Estado de São Paulo - CETESB, Brazil;1. Division of Immunology and Microbiology, Javakhishvili Tbilisi State University, Georgia;2. Tbilisi Medical Academy, Georgia;3. School of Life Sciences, University of Westminster, London, UK;4. University of Georgia, Georgia;5. IQ Clinic, Georgia;1. Faculty of Health & Life Sciences, De Montfort University, UK;2. Department of Respiratory Sciences, University of Leicester, UK;3. Warwick Medical School, University of Warwick, UK;4. Biosciences, Brunel University London, Uxbridge, UK;5. Department of Veterinary Medicine, U.A.E. University, Al Ain, United Arab Emirates;1. Department of Immunology, Medical University of Bialystok, 15-269 Bialystok, Poland;2. Department of Regenerative Medicine and Immune Regulation, Medical University of Bialystok, 15-269 Bialystok, Poland;3. Otolaryngology and Maxillofacial Surgery Ward of the Provincial Integrated Hospital Jedrzej Sniadecki in Bialystok, 15-950 Bialystok, Poland;4. Department of Maxillofacial and Plastic Surgery, Medical University of Bialystok, 15-269 Bialystok, Poland |
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| Abstract: | The blastmodulatory Kit-M, composed of granulocyte-macrophage colony-stimulating-factor (GM-CSF) and Prostaglandin E1 (PGE1), is known to convert myeloid leukaemic blasts (from AML patients) into leukaemia derived dendritic cells (DCleu), which activate immunoreactive cells to gain antileukemic/leukaemia-specific activity. In this study we had a special focus on the influence of Kit-M treated, DC/DCleu containing patients’whole blood (WB, n = 16) on the provision of immunosuppressive regulatory T-cells.We could confirm that Kit-M significantly increased frequencies of (mature) dendritic cells (DC) and DCleu from leukemic whole blood (WB) without induction of blast proliferation. After mixed lymphocyte culture (MLC) with patients’ T-cells we confirmed that DCleu mediated leukemia-specific responses- going along with activated and leukemia-specific T- and NK-cells in an intracellular cytokine staining assay (ICS) and a degranulation assay (Deg)- resulted in an increased anti-leukemic cytotoxicity (Cytotoxicity Fluorolysis Assay = CTX). We could demonstrate that (leukemia-specific) CD4+ and CD8+ regulatory T-cell population (Treg) decreased significantly after MLC compared to controls. We found significant positive correlations of leukemia-specific CD3+CD4+ cells with frequencies of (mature) DCleu. Achieved anti-leukemic cytotoxicity correlated significantly positive with leukemia-specific CD3+CD8+ cells and significantly negatively with (leukemia-specific) Treg.In summary we demonstrate that immunesuppressive (leukemia-specific) regulatory T-cells are significantly downregulated after Kit-M triggered MLC- going along with a (reinstalled) antileukemic reactivity of the immune system (as demonstrated with functional assays ICS, Deg, CTX). |
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| Keywords: | Leukemia derived DC Acute myeloid leukaemia Anti-leukaemic functionality Leukemia-specific cells Regulatory T cells Ø" },{" #name" :" keyword" ," $" :{" id" :" k0035" }," $$" :[{" #name" :" text" ," _" :" on average AML" },{" #name" :" keyword" ," $" :{" id" :" k0045" }," $$" :[{" #name" :" text" ," _" :" acute myeloid leukemia APCs" },{" #name" :" keyword" ," $" :{" id" :" k0055" }," $$" :[{" #name" :" text" ," _" :" antigen presenting cells APC" },{" #name" :" keyword" ," $" :{" id" :" k0065" }," $$" :[{" #name" :" text" ," _" :" allophycocyanin Bla" },{" #name" :" keyword" ," $" :{" id" :" k0075" }," $$" :[{" #name" :" text" ," _" :" blast cells proliferating blasts BM" },{" #name" :" keyword" ," $" :{" id" :" k0095" }," $$" :[{" #name" :" text" ," _" :" bone marrow CAR" },{" #name" :" keyword" ," $" :{" id" :" k0105" }," $$" :[{" #name" :" text" ," _" :" chimeric antigen receptor CCR7" },{" #name" :" keyword" ," $" :{" id" :" k0115" }," $$" :[{" #name" :" text" ," _" :" chemokine receptor 7 CD" },{" #name" :" keyword" ," $" :{" id" :" k0125" }," $$" :[{" #name" :" text" ," _" :" Cluster of Differentiation CD25" },{" #name" :" keyword" ," $" :{" id" :" k0135" }," $$" :[{" #name" :" text" ," _" :" CD25 expression low surface expression of the IL-7 receptor CIK-cells" },{" #name" :" keyword" ," $" :{" id" :" k0155" }," $$" :[{" #name" :" text" ," _" :" cytokine-induced killer cells CR" },{" #name" :" keyword" ," $" :{" id" :" k0165" }," $$" :[{" #name" :" text" ," _" :" Complete Remission CSA" },{" #name" :" keyword" ," $" :{" id" :" k0175" }," $$" :[{" #name" :" text" ," _" :" Cytokine Secretion Assay CTL" },{" #name" :" keyword" ," $" :{" id" :" k0185" }," $$" :[{" #name" :" text" ," _" :" CD8+ cytotoxic lymphocytes CTLA-4" },{" #name" :" keyword" ," $" :{" id" :" k0195" }," $$" :[{" #name" :" text" ," _" :" cytotoxic T-lymphocyte associated Protein CTX" },{" #name" :" keyword" ," $" :{" id" :" k0205" }," $$" :[{" #name" :" text" ," _" :" Cytotoxicity Fluorolysis Assay DC" },{" #name" :" keyword" ," $" :{" id" :" k0215" }," $$" :[{" #name" :" text" ," _" :" Dendritic Cells leukemia-derived Dendritic Cells mature Dendritic Cells Deg" },{" #name" :" keyword" ," $" :{" id" :" k0245" }," $$" :[{" #name" :" text" ," _" :" Degranulation Assay Dgn." },{" #name" :" keyword" ," $" :{" id" :" k0255" }," $$" :[{" #name" :" text" ," _" :" first diagnosis DLI" },{" #name" :" keyword" ," $" :{" id" :" k0265" }," $$" :[{" #name" :" text" ," _" :" Donor Lymphocyte Infusion DMSO" },{" #name" :" keyword" ," $" :{" id" :" k0275" }," $$" :[{" #name" :" text" ," _" :" Dimethysulfoxid ELN" },{" #name" :" keyword" ," $" :{" id" :" k0285" }," $$" :[{" #name" :" text" ," _" :" European Leukemia Network FAB" },{" #name" :" keyword" ," $" :{" id" :" k0295" }," $$" :[{" #name" :" text" ," _" :" French-American-British FACS" },{" #name" :" keyword" ," $" :{" id" :" k0305" }," $$" :[{" #name" :" text" ," _" :" Fluorescence-activated cell sorting 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