THE IMPAIRMENT OF ANTITUMOR CYTOTOXIC ACTIVITY OF DENDRITIC CELLS IN PATIENTS WITH MALIGNANT LYMPHOMA DUE TO THE ALTERED EXPRESSION OF TUMOR NECROSIS FACTOR ALPHA
Abstract
Recent research revealed dendritic cells (DCs) to have direct antitumor cytotoxic activity and to inhibit the growth and proliferation of tumor cells in vitro. The aim of the present study was to investigate the association between the cytotoxic activity of dendritic cells generated in the presence of interferon alpha (IFN-DCs) and TNFα expression by IFN-DCs in patients with malignant lymphomas. It was shown that IFN-DCs of malignant lymphoma patients possessed low cytotoxic activity against tumor cell line HEp-2 associated with low expression of transmembrane TNFα (tmTNFα) and high level of soluble TNFα (sTNFα) secretion. Reduced DC cytotoxic activity and low tmTNFα expression on DC surface were observed mainly in Hodgkin’s lymphoma patients. In contrast, IFN-DCs of patients with non-Hodgkin lymphoma were endowed with the ability to lysis of HEp-2 cells and tmTNFα molecule expression was similar to that in IFN-DCs from healthy donors. It was determined that the increase of expression of tmTNFα molecule on lymphoma patient IFN-DCs induced by the addition of TNFα-converting enzyme inhibitor into IFN-DC cultures was associated with the enhancement of IFN-DC cytotoxic activity against HEp-2 cells.
Supporting agencies: dendritic cells; interferon alpha; lymphomas; tumor necrosis factor alpha
About the Authors
T. V. Tyrinova
Research Institute of Fundamental and Clinical Immunology, Novosibirsk
Russian Federation
Russian Federation
Tyrinova Tamara Viktorovna, PhD, research fellow, Laboratory of Cellular Immunotherapy.
Phone: +7 (383) 228-21-01. E-mail: tyrinova@bk.ru. SPIN-code: 1535-6493
O. Yu. Leplina
Research Institute of Fundamental and Clinical Immunology, Novosibirsk
Russian Federation
Russian Federation
Lepina Olga Yurievna, MD, DSc, Leading researcher, Laboratory of Cellular Immunotherapy.
Phone: +7 (383) 228-21-01. E-mail: oleplina@mail.ru. SPIN-code: 2204-9718
M. A. Tikhonova
Research Institute of Fundamental and Clinical Immunology, Novosibirsk
Russian Federation
Russian Federation
Tikhonova Marina Alexandrovna, Senior research fellow, Laboratory of Cellular Immunotherapy.
Phone: +7 (383) 228-21-01. E-mail: martix-59@mail.ruD. S. Batorova
Research Institute of Fundamental and Clinical Immunology, Novosibirsk
Russian Federation
Russian Federation
Batorova Daria Sergeevna, hematologist, Hematology Department with Bone Marrow Transplantation Unit.
Phone: +7 (383) 228-59-56. E-mail: sugar1983@mail.ruG. Yu. Ushakova
Research Institute of Fundamental and Clinical Immunology, Novosibirsk
Russian Federation
Russian Federation
Ushakova Galina Yurievna, hematologist, Hematology Department with Bone Marrow Transplantation Unit.
Phone: +7 (383) 228-59-56. E-mail: bmt-novosibirsk@mail.ru
V. V. Sergeevicheva
Research Institute of Fundamental and Clinical Immunology, Novosibirsk
Russian Federation
Russian Federation
Sergeevicheva Bera Vasilievna, MD, PhD, Hematology Department with Bone Marrow Transplantation Unit.
Phone: +7 (383) 228-59-56. E-mail: verden@bk.ru. SPINcode: 5507-1870
S. A. Sizikova
Research Institute of Fundamental and Clinical Immunology, Novosibirsk
Russian Federation
Russian Federation
Sizikova Svetlana Anatolievna, MD, PhD, Hematology Department with Bone Marrow Transplantation Unit.
Phone: +7 (383) 228-59-56. E-mail: bmt-novosibirsk@mail.ruI. V. Kryuchkova
Research Institute of Fundamental and Clinical Immunology, Novosibirsk
Russian Federation
Russian Federation
Kruchkova Irina Valentinovna, MD, PhD, Head of Hematology Department with Bone Marrow Transplantation Unit.
Phone: +7 (383) 228-59-56. E-mail: irina_ici@ mail.ru. SPIN-code: 7668-3559A. A. Ostanin
Research Institute of Fundamental and Clinical Immunology, Novosibirsk
Russian Federation
Russian Federation
Ostanin Alexandr Anatolievich, MD, Professor, Principal Investigator, Laboratory of Cellular Immunotherapy.
Phone: +7 (383) 228-21-01. E-mail: ct_lab@mail.ru. SPIN-code: 3199-0970
E. R. Chernykh
Research Institute of Fundamental and Clinical Immunology, Novosibirsk
Russian Federation
Russian Federation
Chernykh Elena Removna, Professor, Corresponding Member of RAS, Head of Cellular Immunotherapy Laboratory.
E-mail: ct_lab@mail.ru. SPIN-code: 8957-0362References
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For citations:
Tyrinova T.V., Leplina O.Yu., Tikhonova M.A., Batorova D.S., Ushakova G.Yu., Sergeevicheva V.V., Sizikova S.A., Kryuchkova I.V., Ostanin A.A., Chernykh E.R. THE IMPAIRMENT OF ANTITUMOR CYTOTOXIC ACTIVITY OF DENDRITIC CELLS IN PATIENTS WITH MALIGNANT LYMPHOMA DUE TO THE ALTERED EXPRESSION OF TUMOR NECROSIS FACTOR ALPHA. Siberian journal of oncology. 2015;1(5):51-58. (In Russ.)
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