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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-CIT-3344</article-id><article-id custom-type="elpub" pub-id-type="custom">mimmun-3344</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>ИЗМЕНЕНИЯ СУБПОПУЛЯЦИОННОГО СОСТАВА И ИММУНОФЕНОТИПИЧЕСКИХ ХАРАКТЕРИСТИК НОРМАЛЬНЫХ ЛИМФОЦИТОВ В КРОВИ БОЛЬНЫХ ХРОНИЧЕСКИМ ЛИМФОЦИТАРНЫМ ЛЕЙКОЗОМ В ДИНАМИКЕ ИММУНОХИМИОТЕРАПИИ</article-title><trans-title-group xml:lang="en"><trans-title>CHANGES IN THE SUBPOPULATION COMPOSITION AND IMMUNOPHENOTYPIC CHARACTERISTICS OF NORMAL LYMPHOCYTES IN THE BLOOD OF PATIENTS WITH CHRONIC LYMPHOCYTIC LEUKEMIA IN THE DYNAMICS OF IMMUNOCHEMOTHERAPY</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0001-6762-0835</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Селютина</surname><given-names>Олеся Николаевна</given-names></name><name name-style="western" xml:lang="en"><surname>Selyutina</surname><given-names>Olesya N.</given-names></name></name-alternatives><bio xml:lang="ru"><p>к.б.н., биолог клинико-диагностической лаборатории</p><p>SPIN: 4347-0302, Author ID: 759134, Scopus Author ID: 57194276434. </p></bio><bio xml:lang="en"><p>Cand. Sci. (Biol.), biologist, Clinical and Diagnostic Laboratory</p><p>Author ID: 759134, Scopus Author ID: 57194276434</p></bio><email xlink:type="simple">selyutinalesya@yandex.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-4222-1579</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Гуськова</surname><given-names>Наиля Катифовна</given-names></name><name name-style="western" xml:lang="en"><surname>Guskova</surname><given-names>Nailya K.</given-names></name></name-alternatives><bio xml:lang="ru"><p>кандидат биологических наук, заведующая клинико-диагностической лабораторией </p></bio><bio xml:lang="en"><p>Cand. Sci. (Biol.), Head of Clinical and Diagnostic Laboratory</p></bio><email xlink:type="simple">guskova.nailya@mail.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-1410-122X</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Златник</surname><given-names>Елена Юрьевна</given-names></name><name name-style="western" xml:lang="en"><surname>Zlatnik</surname><given-names>Elena Yu.</given-names></name></name-alternatives><bio xml:lang="ru"><p>доктор медицинских наук, профессор, главный научный сотрудник лаборатории иммунофенотипирования опухолей</p><p>Author ID (Scopus): 6603160432, SPIN: 4137-7410.</p></bio><bio xml:lang="en"><p>Dr. of Sci. (Med.), Professor, chief researcher of Laboratory of immunophenotyping of tumors</p></bio><email xlink:type="simple">elena-zlatnik@mail.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0003-4457-3815</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Лысенко</surname><given-names>Ирина Борисовна</given-names></name><name name-style="western" xml:lang="en"><surname>Lysenko</surname><given-names>Irina B.</given-names></name></name-alternatives><bio xml:lang="ru"><p>доктор медицинских наук, профессор, заведующая отделением онкогематологии</p></bio><bio xml:lang="en"><p>Dr. of Sci. (Med.), Professor, Head of the Department of Oncohematology</p></bio><email xlink:type="simple">iralyss@rambler.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-3561-098X</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Дженкова</surname><given-names>Елена Алексеевна</given-names></name><name name-style="western" xml:lang="en"><surname>Dzhenkova</surname><given-names>Elena A.</given-names></name></name-alternatives><bio xml:lang="ru"><p>д.б.н., профессор, ученый секретарь</p><p>AuthorID: 697354, ResearcherID: K-9622-2014, Scopus Author ID: 6507889745.</p></bio><bio xml:lang="en"><p>Dr. Sci. (Biol.), Professor, scientific Secretary</p></bio><email xlink:type="simple">rnioi@list.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-4822-5044</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Владимирова</surname><given-names>Любовь Юрьевна</given-names></name><name name-style="western" xml:lang="en"><surname>Vladimirova</surname><given-names>Lyubov Yu.</given-names></name></name-alternatives><bio xml:lang="ru"><p>д.м.н., профессор, заведующая отделом лекарственного лечения опухолей</p><p>Scopus Author ID: 7004401163.              </p></bio><bio xml:lang="en"><p>Dr. of Sci. (Med.), Professor, Head of the Department of Drug Treatment of Tumors</p></bio><email xlink:type="simple">rnioi@list.ru</email><xref ref-type="aff" rid="aff-1"/></contrib></contrib-group><aff-alternatives id="aff-1"><aff xml:lang="ru">ФГБУ «Национальный медицинский исследовательский центр онкологии» Минздрава России, Российская Федерация, г. Ростов-на-Дону<country>Россия</country></aff><aff xml:lang="en">National Medical Research Centre for Oncology, Ministry of Health of Russia, Rostov-on-Don, Russia<country>Russian Federation</country></aff></aff-alternatives><pub-date pub-type="collection"><year>2019</year></pub-date><pub-date pub-type="epub"><day>18</day><month>02</month><year>2026</year></pub-date><volume>0</volume><issue>0</issue><issue-title>Online First</issue-title><elocation-id>3344</elocation-id><permissions><copyright-statement>Copyright &amp;#x00A9; Селютина О.Н., Гуськова Н.К., Златник Е.Ю., Лысенко И.Б., Дженкова Е.А., Владимирова Л.Ю., 2019</copyright-statement><copyright-year>2019</copyright-year><copyright-holder xml:lang="ru">Селютина О.Н., Гуськова Н.К., Златник Е.Ю., Лысенко И.Б., Дженкова Е.А., Владимирова Л.Ю.</copyright-holder><copyright-holder xml:lang="en">Selyutina O.N., Guskova N.K., Zlatnik E.Y., Lysenko I.B., Dzhenkova E.A., Vladimirova L.Y.</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/3344">https://www.mimmun.ru/mimmun/article/view/3344</self-uri><abstract><p>При хроническом лимфоцитарном лейкозе (ХЛЛ) прогрессирующее нарушение иммунной системы приводит к состоянию клинически выраженной иммунной супрессии и отсутствию контроля над заболеванием. Как следствие, иммунологические изменения в субпопуляциях нормальных лимфоцитов в крови больных хроническим лимфоцитарным лейкозом могут играть негативную роль в прогрессировании заболевания. Целью исследования было изучение влияния иммунохимиотерапии на субпопуляционный состав и иммунофенотипические характеристики нормальных лимфоцитов в крови больных ХЛЛ. В исследование включены 37 мужчин и 25 женщин с впервые диагностированным ХЛЛ в стадии B и С по Binet, медиана возраста 64 [50; 71] года, получивших по 6 циклов иммунохимиотерапии в двух режимах: RB (Ритуксимаб+Бендамустин) или FCR (Ритуксимаб+Флударабин+Циклофосфамид). В крови больных до- и после лечения исследован субпопуляционный состав поликлональных В-лимфоцитов, Т-лимфоцитов (Т-хелперы, Т-регуляторные клетки, Т-цитотоксические клетки), NK-клетки, а также экспрессия на них рецепторов иммунных контрольных точек PD1, PD-L1, LAG3. Исследования выполняли с применением метода 10-цветной проточной цитометрии (Navios 10/3, Beckman Coulter, США). Статистический анализ выполнен в программе Statistica 13.0. Проведенное исследование показало, что у всех больных ХЛЛ до- и после иммунохимиотерапии отмечаются значимые количественные и функциональные изменения субпопуляционного состава В- лимфоцитов, Т-лимфоцитов и NK клеток. Доля нормальных поликлональных В-клеток среди всех лимфоцитов до лечения снижена и характеризуется экспрессией PD1. Проведение терапии приводит к частичному восстановлению популяции нормальных В-лимфоцитов, на которых не выявляется экспрессия PD1, PD-L1, LAG3. Изменение иммунофенотипических характеристик субпопуляций Т- лимфоцитов носит однонаправленный характер. До лечения и после его завершения, на CD4+ и CD8+ Т-клетках наблюдается наиболее высокая экспрессия PD1, что свидетельствует о нарушении их противоопухолевых функций. После лечения, Т-лимфоцитарное микроокружение приобретает тенденцию к восстановлению за счет увеличения их количества. Однако сохранение на Т-клетках экспрессии молекулы PD1, по-видимому, препятствует полному восстановлению их функциональной активности, что, наряду с повышением содержания Т-регуляторных клеток и сохранением на NK-лимфоцитах ингибирующих молекул PD1 и LAG3, в совокупности, способствует подавлению противоопухолевого иммунного ответа и снижению возможности обеспечения длительной ремиссии.  В этой связи, мониторинг иммунологических показателей в процессе проведения иммунохимиотерапии полезен для выявления степени дисрегуляции иммунного ответа и, тем самым, для своевременного оказания наряду с противоопухолевой терапией и корригирующей иммунотерапии.</p></abstract><trans-abstract xml:lang="en"><p>Immunological changes in subpopulations of normal lymphocytes in the blood of patients with chronic lymphocytic leukemia (CLL) may play a negative role in the progression of the disease. The aim - to study the effect of immunochemotherapy on the subpopulation composition and immunophenotypic characteristics of normal lymphocytes in the blood of patients with CLL. The study included 37 men, 25 women with CLL in stages B, C according to Binet, median age 64 [50; 71] years old, who received 6 cycles of immunochemotherapy: RB (Rituximab+Bendamustine) or FCR (Rituximab+Fludarabine+ Cyclophosphamide). The subpopulation composition of polyclonal B-, T- (T helper cells, T regulatory cells, T cytotoxic cells), NK-lymphocytes, as well as the expression of PD1, PD-L1, LAG3 were studied in the blood of patients before and after treatment. The studies were performed using the method of flow cytometry (Navios 10/3, Beckman Coulter, USA). The statistical analysis is performed in Statistica 13.0. The study showed that all patients with CLL had significant quantitative and functional changes in the subpopulation composition of B-, T-, and NK-lymphocytes before and after therapy. The proportion of normal polyclonal B cells among all lymphocytes before treatment is reduced and is characterized by PD1 expression. The therapy leads to a partial restoration of the population of normal B-lymphocytes, which do not show expression of PD1, PD-L1, LAG3. Before and after treatment, CD4+ and CD8+ T cells show the highest expression of PD1, which indicates a violation of their antitumor functions. After treatment, the T-lymphocyte microenvironment tends to recover due to an increase in their number. However, the preservation of PD1 expression on T-cells apparently prevents the complete restoration of their functional activity, which, along with an increase in the content of T-regulatory cells and the preservation of PD1 and LAG3 expression on NK-lymphocytes, helps to suppress the antitumor immune response and reduce the possibility of long-term remission. In this regard, monitoring of immunological parameters during therapy is useful for detecting the degree of dysregulation of the immune response and, thus, for timely provision along with antitumor therapy and corrective immunotherapy.</p></trans-abstract><kwd-group xml:lang="ru"><kwd>хронический лимфоцитарный лейкоз</kwd><kwd>субпопуляции лимфоцитов</kwd><kwd>иммунные контрольные точки</kwd><kwd>PD1</kwd><kwd>PD-L1</kwd><kwd>LAG3</kwd><kwd>иммунохимиотерапия.</kwd></kwd-group><kwd-group xml:lang="en"><kwd>chronic lymphocytic leukemia</kwd><kwd>lymphocyte subpopulations</kwd><kwd>immune checkpoints</kwd><kwd>PD1</kwd><kwd>PD-L1</kwd><kwd>LAG3</kwd><kwd>immunochemotherapy.</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">Ключагина, Ю.И., Соколова З.А., Барышникова М.А. 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