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<article article-type="research-article" dtd-version="1.3" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xml:lang="ru"><front><journal-meta><journal-id journal-id-type="publisher-id">mimmun</journal-id><journal-title-group><journal-title xml:lang="ru">Медицинская иммунология</journal-title><trans-title-group xml:lang="en"><trans-title>Medical Immunology (Russia)</trans-title></trans-title-group></journal-title-group><issn pub-type="ppub">1563-0625</issn><issn pub-type="epub">2313-741X</issn><publisher><publisher-name>SPb RAACI</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.15789/1563-0625-2016-2-151-162</article-id><article-id custom-type="elpub" pub-id-type="custom">mimmun-998</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="ru"><subject>ОРИГИНАЛЬНЫЕ СТАТЬИ</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="en"><subject>ORIGINAL ARTICLES</subject></subj-group></article-categories><title-group><article-title>ЦИРКУЛИРУЮЩИЙ БЕЛОК MICА У БОЛЬНЫХ ЗЛОКАЧЕСТВЕННЫМИ ЛИМФОМАМИ</article-title><trans-title-group xml:lang="en"><trans-title>CIRCULATING MICA PROTEIN IN PATIENTS WITH MALIGNANT LYMPHOMAS</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Клинкова</surname><given-names>А. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Klinkova</surname><given-names>A. V.</given-names></name></name-alternatives><bio xml:lang="ru"><p>младший научный сотрудник, лаборатория клеточных взаимодействий,</p><p>117997, Москва, ул. Миклухо-Маклая, 16/10</p></bio><bio xml:lang="en"><p>Junior Research Associate, Laboratory of Cell Interactions,</p><p>117997, Moscow, Miklukho-Maklaya str., 16/10</p></bio><email xlink:type="simple">lenkovalen@mail.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Кузьмина</surname><given-names>Е. Г.</given-names></name><name name-style="western" xml:lang="en"><surname>Kuzmina</surname><given-names>E. G.</given-names></name></name-alternatives><bio xml:lang="ru"><p>к.б.н., заведующая лабораторией клинической иммунологии,</p><p>г. Обнинск, Калужская область</p></bio><bio xml:lang="en"><p>PhD (Biology), Head, Laboratory of Clinical Immunology,</p><p>Obninsk, Kaluga Region</p></bio><xref ref-type="aff" rid="aff-2"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Абакушина</surname><given-names>Е. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Abakushina</surname><given-names>E. V.</given-names></name></name-alternatives><bio xml:lang="ru"><p>к.м.н., старший научный сотрудник, лаборатория клинической иммунологии,</p><p>г. Обнинск, Калужская область</p></bio><bio xml:lang="en"><p>PhD (Biology), Head, Laboratory of Clinical Immunology,</p><p>Obninsk, Kaluga Region</p></bio><xref ref-type="aff" rid="aff-2"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Каневский</surname><given-names>Л. М.</given-names></name><name name-style="western" xml:lang="en"><surname>Kanevskiy</surname><given-names>L. M.</given-names></name></name-alternatives><bio xml:lang="ru"><p>к.б.н., научный сотрудник, лаборатория клеточных взаимодействий,</p><p>Москва</p></bio><bio xml:lang="en"><p>PhD (Biology), Research Associate, Laboratory of Cell Interactions,</p><p>Moscow</p></bio><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Неприна</surname><given-names>Г. С.</given-names></name><name name-style="western" xml:lang="en"><surname>Neprina</surname><given-names>G. S.</given-names></name></name-alternatives><bio xml:lang="ru"><p>к.м.н., ведущий научный сотрудник, лаборатория клинической иммунологии,</p><p>г. Обнинск, Калужская область</p></bio><bio xml:lang="en"><p>PhD (Medicine), Leading Research Associate, Laboratory of Clinical Immunology,</p><p>Obninsk, Kaluga Region</p></bio><xref ref-type="aff" rid="aff-2"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Павлов</surname><given-names>В. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Pavlov</surname><given-names>V. V.</given-names></name></name-alternatives><bio xml:lang="ru"><p>к.м.н., заведующий отделением лучевой и лекарственной терапии гемобластозов,</p><p>г. Обнинск, Калужская область</p></bio><bio xml:lang="en"><p>PhD (Medicine), Head, Department of Radiation and Drug Therapy of Leukemia,</p><p>Obninsk, Kaluga Region</p></bio><xref ref-type="aff" rid="aff-2"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Коваленко</surname><given-names>Е. И.</given-names></name><name name-style="western" xml:lang="en"><surname>Kovalenko</surname><given-names>E. I.</given-names></name></name-alternatives><bio xml:lang="ru"><p>к.б.н., старший научный сотрудник, лаборатория клеточных взаимодействий,</p><p>Москва</p></bio><bio xml:lang="en"><p>PhD (Biology), Senior Research Associate, Laboratory of Cell Interactions,</p><p>Moscow</p></bio><xref ref-type="aff" rid="aff-1"/></contrib></contrib-group><aff-alternatives id="aff-1"><aff xml:lang="ru">ФГБУН «Институт биоорганической химии им. акад. М.М. Шемякина и Ю.А. Овчинникова» РАН<country>Россия</country></aff><aff xml:lang="en">Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences<country>Russian Federation</country></aff></aff-alternatives><aff-alternatives id="aff-2"><aff xml:lang="ru">Медицинский радиологический научный центр им. А.Ф. Цыба – филиал ФГБУ «Национальный исследовательский радиологический центр» Министерства здравоохранения РФ<country>Россия</country></aff><aff xml:lang="en">A. Tsyb Medical Radiological Research Centre, affiliated to the National Medical Radiological Research Centre, Ministry of Healthcare of the Russian Federation<country>Russian Federation</country></aff></aff-alternatives><pub-date pub-type="collection"><year>2016</year></pub-date><pub-date pub-type="epub"><day>14</day><month>04</month><year>2016</year></pub-date><volume>18</volume><issue>2</issue><fpage>151</fpage><lpage>162</lpage><permissions><copyright-statement>Copyright &amp;#x00A9; Клинкова А.В., Кузьмина Е.Г., Абакушина Е.В., Каневский Л.М., Неприна Г.С., Павлов В.В., Коваленко Е.И., 2016</copyright-statement><copyright-year>2016</copyright-year><copyright-holder xml:lang="ru">Клинкова А.В., Кузьмина Е.Г., Абакушина Е.В., Каневский Л.М., Неприна Г.С., Павлов В.В., Коваленко Е.И.</copyright-holder><copyright-holder xml:lang="en">Klinkova A.V., Kuzmina E.G., Abakushina E.V., Kanevskiy L.M., Neprina G.S., Pavlov V.V., Kovalenko E.I.</copyright-holder><license license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>This work is licensed under a Creative Commons Attribution 4.0 License.</license-p></license></permissions><self-uri xlink:href="https://www.mimmun.ru/mimmun/article/view/998">https://www.mimmun.ru/mimmun/article/view/998</self-uri><abstract><p>Белок MICA – это стресс-индуцированный белок, который, как правило, не экспрессируется в здоровых тканях, однако появляется в большом количестве на поверхности клеток, подвергшихся опухолевой трансформации. В организме человека этот белок может как инициировать противоопухолевый иммунный ответ, так и способствовать ускользанию опухолевых клеток от уничтожения. В результате сбрасывания с поверхности опухолевых клеток растворимый белок MICA попадает в циркуляцию и способствует снижению активности эффекторных клеток за счет инактивации рецептора NKG2D. В данном исследовании была поставлена задача определить различия в концентрации циркулирующего белка sMICA в сыворотке крови больных разными типами злокачественных лимфом и оценить влияние sMICA на NKG2D-позитивные цитотоксические лимфоциты. В экспериментальной модели с использованием клеточной линии C1R-MICA показан феномен сбрасывания MICA с поверхности культивируемых опухолевых клеток во внеклеточное пространство и продемонстрировано с помощью проточной цитометрии снижение экспрессии в мононуклеарах периферической крови рецептора NKG2D, зависимое от содержания sMICA в культуральной среде, что предполагает участие сывороточных молекул sMICA в супрессии противоопухолевого иммунного ответа. С помощью иммуноферментного метода проведен анализ содержания циркулирующего белка sMICA у больных с различными типами В-клеточных и Т-клеточной неходжкинскими лимфомами и выявлены группы пациентов с повышенным, по сравнению с контрольной группой, содержанием циркулирующего sMICA. Минимальное количество сывороточного sMICA было зарегистрировано в контрольной группе с медианой 20 пг/мл. В объединенной группе больных различными В-клеточными лимфомами было выявлено увеличение концентрации циркулирующего белка MICA более чем в 6,5 раз по сравнению с контрольной группой. При этом наиболее высокие значения sMICA были зарегистрированы в группах пациентов с хроническим лимфолейкозом, диффузной В-крупноклеточной лимфомой и множественной миеломой. Максимальное увеличение уровня растворимого белка sMICA среди исследованных групп больных наблюдалось в группе больных Т-клеточной анапластической лимфомой (медиана 574 пг/мл). В исследовании получены предварительные данные, свидетельствующие о супрессирующем влиянии разных компонентов (иммуно)полихимиотерапии, в частности ритуксимаба и лучевой терапии лимфом на уровень сывороточного sMICA. Таким образом, повышенный уровень sMICA у онкогематологических больных может явиться дополнительным основанием для применения противоопухолевой терапии, а мониторинг уровня sMICA на разных этапах лечения может оказаться полезен для оценки ее эффективности.</p></abstract><trans-abstract xml:lang="en"><p>MICA is a stress-induced protein that, as a rule, is not expressed in healthy tissues, but appears in large amounts on the surface of cells undergoing malignant transformation. In humans, this protein can either initiate antitumor immune response, or facilitate tumor cells for their escape of destruction. After shedding from tumor cell surface, soluble MICA enters blood circulation and contributes to decreased activity of effector cells, due to inactivation of NKG2D receptor. The aim of our study was to determine differences in circulating sMICA concentrations in sera of patients with different types of malignant lymphomas, and to evaluate the impact of sMICA upon NKG2D-positive cytotoxic lymphocytes. In experimental models with C1R-MICA cells, the MICA shedding was shown to occur from the surface of cultured tumor cells into the extracellular space. A reduced NKG2D expression dependent on sMICA concentration in the culture medium was demonstrated by flow cytometry in peripheral mononuclear cells, thus suggesting a role of serum sMICA in suppression of antitumor immune response. The sMICA detection was performed in patients with various types of B- or T-cell non-Hodgkin’s lymphomas by means of enzyme-linked immunosorbent assay. The groups of patients with increased sMICA content were identified and compared with the control group. Minimal amounts of serum sMICA were registered in the control group, with the median of 20 pg/ml. In a combined group of patients with various B-cell lymphomas, an increase in circulating sMICA amounts was shown, at the levels of more than 6.5 times exceeding the control values. The highest values of sMICA were recorded among the patients with chronic lymphocytic leukemia, diffuse large cell lymphoma, and multiple myeloma. Maximal sMICA levels among the investigated groups of patients were observed in the group of patients with T-cell anaplastic lymphoma (median of 574 pg/ml). The study provides preliminary evidence for a suppressive effect of different (immuno)chemotherapy components, in particular, rituximab and radiation therapy, upon serum sMICA contents in the lymphoma patients. Thus, elevated serum sMICA levels in patients with hematological malignancies may be considered as an additional criterion for application of the antitumor therapy. sMICA monitoring at different stages of cytostatic treatment may be useful in order to evaluate its efficiency.</p></trans-abstract><kwd-group xml:lang="ru"><kwd>злокачественные лимфомы</kwd><kwd>лимфопролиферативные заболевания</kwd><kwd>белок MICA</kwd><kwd>sMICA</kwd><kwd>цитотоксические лимфоциты</kwd><kwd>рецептор NKG2D</kwd></kwd-group><kwd-group xml:lang="en"><kwd>malignant lymphomas</kwd><kwd>lymphoproliferative diseases</kwd><kwd>MICA protein</kwd><kwd>sMICA</kwd><kwd>cytotoxic lymphocytes</kwd><kwd>NKG2D receptor</kwd></kwd-group></article-meta></front><back><ref-list><title>References</title><ref id="cit1"><label>1</label><citation-alternatives><mixed-citation xml:lang="ru">Абакушина Е.В., Абакушин Д.Н., Неприна Г.С., Пасова И.А., Бердов Б.А., Клинкова А.В., Коваленко Е.И., Каприн А.Д. 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