Phenotypic and functional changes of NK cells in patients with myelodysplastic syndrome and acute myeloid leukemia treated with hypomethylating drugs

Natural killer cells (NK cells) are cytotoxic lymphocytes that play a pivotal role in maintaining immunological surveillance and in developing an innate immune response. Since the discovery of NK cells in 1973, the mechanisms of their functioning have been studied in details, and there is currently...

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Autores principales:	D. I. Zhigarev, M. V. Khoreva, L. V. Gankovskaya
Formato:	article
Lenguaje:	RU
Publicado:	SPb RAACI 2021
Materias:	nk cells antitumor immunity acute myeloid leukemia myelodysplastic syndrome kir receptors hypomethylating drugs Immunologic diseases. Allergy RC581-607
Acceso en línea:	https://doaj.org/article/0ac3750ff0b140068bb55da5c79d3647
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spelling	oai:doaj.org-article:0ac3750ff0b140068bb55da5c79d36472021-11-18T08:03:50ZPhenotypic and functional changes of NK cells in patients with myelodysplastic syndrome and acute myeloid leukemia treated with hypomethylating drugs1563-06252313-741X10.15789/1563-0625-PAF-2145https://doaj.org/article/0ac3750ff0b140068bb55da5c79d36472021-05-01T00:00:00Zhttps://www.mimmun.ru/mimmun/article/view/2145https://doaj.org/toc/1563-0625https://doaj.org/toc/2313-741XNatural killer cells (NK cells) are cytotoxic lymphocytes that play a pivotal role in maintaining immunological surveillance and in developing an innate immune response. Since the discovery of NK cells in 1973, the mechanisms of their functioning have been studied in details, and there is currently no doubt that they play a special role in the process of recognition and destruction of transformed and malignant cells. Understanding the role of NK cells in antitumor immunity, on the one hand, leads to emergence of new immunotherapeutic strategies and, on the other hand, allows to adjust the existing treatment regimens for tumor diseases, in accordance with the principle of primum non nocere. Optimization of cancer therapy protocols executed in order to protect immune cells from death and functional impairment is an important problem that cannot be successfully resolved without regular aggregation of the results from disparate studies and critical analysis of the all accumulated data.The objective of this review is to create a relevant and holistic picture of changes in the phenotypic and functional characteristics of NK cells in patients with two related hematological diseases – myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). For the treatment of both illnesses, drugs from the group of hypomethylating agents are used, the acting mechanism of which, unlike classical cytostatic agents, is based on modulation of the tumor cell genes expression. All the cells of the body are being affected, including NK cells, since these drugs act nonspecifically. Such an interaction leads to a hypomethylation of NK cell DNA and changes the expression of functional receptors, which, in turn, provide the development of antitumor NK cell immune response.Of course, just the fact of changing gene expression in certain cells does not allow us to fully judge the drug’s impact on the state of immune system. Meanwhile, the origin of this change and its role are important in the context of the disease pathogenesis. Ultimately, a simple description of an increase or decrease in a single receptor expression is not illustrative, since it can lead to uncertain consequences. For this reason, the current review, in addition to describing the existing data on the changes of NK cell receptors expression under the influence of hypomethylating drugs, gives a special attention to critical analysis of functional characteristics of NK cells, including their cytotoxic activity aimed at malignant blast cells, being a determinant of clinical course in the described diseases.D. I. ZhigarevM. V. KhorevaL. V. GankovskayaSPb RAACIarticlenk cellsantitumor immunityacute myeloid leukemiamyelodysplastic syndromekir receptorshypomethylating drugsImmunologic diseases. AllergyRC581-607RUMedicinskaâ Immunologiâ, Vol 23, Iss 2, Pp 223-230 (2021)
institution	DOAJ
collection	DOAJ
language	RU
topic	nk cells antitumor immunity acute myeloid leukemia myelodysplastic syndrome kir receptors hypomethylating drugs Immunologic diseases. Allergy RC581-607
spellingShingle	nk cells antitumor immunity acute myeloid leukemia myelodysplastic syndrome kir receptors hypomethylating drugs Immunologic diseases. Allergy RC581-607 D. I. Zhigarev M. V. Khoreva L. V. Gankovskaya Phenotypic and functional changes of NK cells in patients with myelodysplastic syndrome and acute myeloid leukemia treated with hypomethylating drugs
description	Natural killer cells (NK cells) are cytotoxic lymphocytes that play a pivotal role in maintaining immunological surveillance and in developing an innate immune response. Since the discovery of NK cells in 1973, the mechanisms of their functioning have been studied in details, and there is currently no doubt that they play a special role in the process of recognition and destruction of transformed and malignant cells. Understanding the role of NK cells in antitumor immunity, on the one hand, leads to emergence of new immunotherapeutic strategies and, on the other hand, allows to adjust the existing treatment regimens for tumor diseases, in accordance with the principle of primum non nocere. Optimization of cancer therapy protocols executed in order to protect immune cells from death and functional impairment is an important problem that cannot be successfully resolved without regular aggregation of the results from disparate studies and critical analysis of the all accumulated data.The objective of this review is to create a relevant and holistic picture of changes in the phenotypic and functional characteristics of NK cells in patients with two related hematological diseases – myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). For the treatment of both illnesses, drugs from the group of hypomethylating agents are used, the acting mechanism of which, unlike classical cytostatic agents, is based on modulation of the tumor cell genes expression. All the cells of the body are being affected, including NK cells, since these drugs act nonspecifically. Such an interaction leads to a hypomethylation of NK cell DNA and changes the expression of functional receptors, which, in turn, provide the development of antitumor NK cell immune response.Of course, just the fact of changing gene expression in certain cells does not allow us to fully judge the drug’s impact on the state of immune system. Meanwhile, the origin of this change and its role are important in the context of the disease pathogenesis. Ultimately, a simple description of an increase or decrease in a single receptor expression is not illustrative, since it can lead to uncertain consequences. For this reason, the current review, in addition to describing the existing data on the changes of NK cell receptors expression under the influence of hypomethylating drugs, gives a special attention to critical analysis of functional characteristics of NK cells, including their cytotoxic activity aimed at malignant blast cells, being a determinant of clinical course in the described diseases.
format	article
author	D. I. Zhigarev M. V. Khoreva L. V. Gankovskaya
author_facet	D. I. Zhigarev M. V. Khoreva L. V. Gankovskaya
author_sort	D. I. Zhigarev
title	Phenotypic and functional changes of NK cells in patients with myelodysplastic syndrome and acute myeloid leukemia treated with hypomethylating drugs
title_short	Phenotypic and functional changes of NK cells in patients with myelodysplastic syndrome and acute myeloid leukemia treated with hypomethylating drugs
title_full	Phenotypic and functional changes of NK cells in patients with myelodysplastic syndrome and acute myeloid leukemia treated with hypomethylating drugs
title_fullStr	Phenotypic and functional changes of NK cells in patients with myelodysplastic syndrome and acute myeloid leukemia treated with hypomethylating drugs
title_full_unstemmed	Phenotypic and functional changes of NK cells in patients with myelodysplastic syndrome and acute myeloid leukemia treated with hypomethylating drugs
title_sort	phenotypic and functional changes of nk cells in patients with myelodysplastic syndrome and acute myeloid leukemia treated with hypomethylating drugs
publisher	SPb RAACI
publishDate	2021
url	https://doaj.org/article/0ac3750ff0b140068bb55da5c79d3647
work_keys_str_mv	AT dizhigarev phenotypicandfunctionalchangesofnkcellsinpatientswithmyelodysplasticsyndromeandacutemyeloidleukemiatreatedwithhypomethylatingdrugs AT mvkhoreva phenotypicandfunctionalchangesofnkcellsinpatientswithmyelodysplasticsyndromeandacutemyeloidleukemiatreatedwithhypomethylatingdrugs AT lvgankovskaya phenotypicandfunctionalchangesofnkcellsinpatientswithmyelodysplasticsyndromeandacutemyeloidleukemiatreatedwithhypomethylatingdrugs
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Phenotypic and functional changes of NK cells in patients with myelodysplastic syndrome and acute myeloid leukemia treated with hypomethylating drugs

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