mimmunМедицинская иммунологияMedical Immunology (Russia)1563-06252313-741XSPb RAACI10.15789/1563-0625-GCI-2624mimmun-2624Research ArticleОРИГИНАЛЬНЫЕ СТАТЬИORIGINAL ARTICLESγδT-клетки у пациентов с опухолями полости носа и околоносовых пазухγδT cells in patients with tumors of the nasal cavity and paranasal sinuseshttps://orcid.org/0000-0003-1633-7487НижегородоваД. Б.NizheharodavaD. B.

Нижегородова Дарья Борисовна – кандидат биологических наук, доцент, ведущий научный сотрудник отдела иммунологии и биомедицинских технологий научно-исследовательской лаборатории, БМАПО; доцент кафедры иммунологии, МГЭИ им. А.Д. Сахарова БГУ.

220013, Минск, ул. П. Бровки 3, корп. 3

Тел.: +375 296089994

Darya B. Nizheharodava - PhD (Biology), Associate Professor, Leading Research Associate, Immunology and Biomedical Technologies Department of Central Research Laboratory, Belarusian Medical Academy of Postgraduate Education; Associate Professor, Immunology Department, International Sakharov Environmental Institute of Belarusian State University.

3 P. Brovki St, Bldg 3 220013, Minsk 220013

Phone: +375 296089994

nzh@tut.byКолядичЖ. В.KolyadichJ. V.

Доктор медицинских наук, профессор, заведующая лабораторией онкопатологии центральной нервной системы с группой онкопатологии головы и шеи.

Минский район, а/г Лесной

Janna V. Kolyadich - PhD, MD (Medicine), Professor, Head, Laboratory of Oncopathology of the Central Nervous System with a Group of Oncopathology of the Head and Neck, N. Alexandrov National Cancer Centre of Belarus.

Minsk District

janept@list.ruМорозоваН. А.MarozavaN. A.

Аспирант, врач – онколог-хирург отделения опухолей головы и шеи.

Минский район, а/г Лесной

Natallia A. Marozava - Postgraduate student, Oncologist-Surgeon, Head and Neck Tumors Department, N. Alexandrov National Cancer Centre of Belarus.

Minsk District

natalim-22@yandex.ruhttps://orcid.org/0000-0002-8739-8300ЗафранскаяМ. М.ZafranskayaM. M.

Доктор медицинских наук, профессор, главный научный сотрудник отдела иммунологии и биомедицинских технологий научно-исследовательской лаборатории, БМАПО; заведующая кафедрой иммунологии, МГЭИ им. А.Д. Сахарова БГУ.

Минск

Marina M. Zafranskaya - PhD, MD (Medicine), Professor, Chief Research Associate, Immunology and Biomedical Technologies Department of Central Research Laboratory, Belarusian Medical Academy of Postgraduate Education; Head, Immunology Department, International Sakharov Environmental Institute of Belarusian State University.

Minsk

zafranskaya@gmail.comБелорусская медицинская академия последипломного образования; Международный государственный экологический институт имени А.Д. Сахарова Белорусского государственного университетаБеларусьBelarusian Medical Academy of Postgraduate Education; International Sakharov Environmental Institute of Belarusian State UniversityBelarusРеспубликанский научно-практический центр онкологии и медицинской радиологии имени Н.Н. АлександроваБеларусьN. Alexandrov National Cancer Centre of BelarusBelarus20231710202325613431352Copyright © Нижегородова Д.Б., Колядич Ж.В., Морозова Н.А., Зафранская М.М., 20232023Нижегородова Д.Б., Колядич Ж.В., Морозова Н.А., Зафранская М.М.Nizheharodava D.B., Kolyadich J.V., Marozava N.A., Zafranskaya M.M.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.mimmun.ru/mimmun/article/view/2624

Иммунологические факторы могут играть важную роль в качестве предикторов или прогностических биомаркеров при онкопатологических процессах. В последнее время в качестве перспективных эффекторных клеток для иммунотерапии злокачественных новообразований рассматривается популяция неклассических γδT-лимфоцитов, сочетающих свойства врожденного и приобретенного иммунитета. В данной работе представлена структурно-функциональная характеристика субпопуляций γδT-лимфоцитов, вовлекающихся в формирование противоопухолевого иммунитета у пациентов со злокачественными и доброкачественными опухолями полости носа и околоносовых пазух. Цель исследования – оценить субпопуляционный состав и функциональные особенности γδТ-клеток у пациентов с новообразованиями полости носа и околоносовых пазух для характеристики механизмов клеточного иммунитета при опухоль-ассоциированном патологическом процессе.

Материалом исследования явилась периферическая венозная кровь 21 пациента (13 мужчин и 8 женщин, средний возраст 63,0 (56,0-69,0) лет) с новообразованиями полости носа и околоносовых пазух и 10 условно здоровых доноров. Фенотип лимфоидных клеток и внутриклеточную продукцию цитокинов оценивали с использованием моноклональных антител и метода проточной цитометрии, внеклеточную продукцию цитокинов исследовали в супернатантах культур методом иммуноферментного анализа.

Установлено увеличение общего количества γδТ-клеток у пациентов с плоскоклеточным раком и изменение соотношения Vδ2+/Vδ1+Т-клеток в периферической крови как у пациентов со злокачественными, так и доброкачественными опухолями полости носа и околоносовых пазух по сравнению со здоровыми донорами. В обеих исследуемых группах пациентов выявлено повышение уровня фосфоантиген-индуцируемой активации γδТ-клеток в сочетании со снижением индексов стимуляции и различным цитокиновым профилем: у пациентов с плоскоклеточным раком отмечалось увеличение внутриклеточной продукции IFNγ в γδТ-клетках, в то время как у пациентов с инвертированной папилломой перераспределение субпопуляций γδT-лимфоцитов связано с преимущественной продукцией IL-17. При этом процент γδT-лимфоцитов, синтезирующих IFNγ, коррелировал с его концентрацией в супернатантах клеточных культур у пациентов со злокачественными новообразованиями полости носа и околоносовых пазух (R = 0,61; p < 0,05).

Полученные данные свидетельствуют о вовлечении γδT-лимфоцитов в патогенез злокачественных и доброкачественных опухолей и могут являться фундаментальной основой для дальнейшего определения возможных предикторов опухоль-ассоциированной воспалительной реакции и малигнизации.

The immunological factors can play an important role as predictive and prognostic biomarkers in oncopathology. Recently, non-conventional innate-like γδT-lymphocytes have received a lot of attention as a promising effector cell population for cancer immunotherapy. This study describes structural and functional subpopulations of γδT lymphocytes involved in antitumor immunity in patients with malignant and benign tumors of the nasal cavity and paranasal sinuses. The aim of the study was to estimate γδT cell subsets composition and functions in patients with neoplasms of nasal cavity and paranasal sinuses in order to characterize cellular immunity in tumor-associated pathological process.

The peripheral venous blood was obtained from 21 patients (13 men and 8 women, average age of 63.0 (56.0-69.0) y. o.) with neoplasms of nasal cavity and paranasal sinuses, and 10 healthy donors. Lymphoid cells phenotype and production of intracellular cytokines were investigated using monoclonal antibodies and flow cytometry, production of extracellular cytokines was measured using enzyme-linked immunosorbent assay kits.

The increase of total γδT cells number in patients with squamous cell carcinoma accompanied by changes in Vγ2+/Vγ1+T cells ratio in peripheral blood of both patients’ groups with malignant and benign nasal cavity and paranasal sinuses tumors were revealed as compared to healthy donors. The upregulated γδT cell response to phosphoantigen induction in combination with reduced indices of stimulations were shown in the both patients groups but cytokine profile was different, i.e., the elevated IFNγ production has been determined in patients with squamous cell carcinoma. However, in patients with inverted papilloma, redistribution of γδT cell subsets has been associated with IL-17-producing γδT cells. Moreover, the percent of IFNγ+γδT lymphocytes did correlate with IFNγ concentration in cell culture supernatants of patients with malignant nasal cavity and paranasal sinuses neoplasms (R = 0.61; p < 0.05).

The revealed data suggest an involvement of γδT lymphocytes in malignant and benign tumor pathogenesis and may provide a fundamental basis for further detection of possible tumor-associated inflammation and malignization predictors.

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The authors declare that there are no conflicts of interest present.