oncotomskСибирский онкологический журналSiberian journal of oncology1814-48612312-3168Tomsk National Research Medical Сепtеr of the Russian Academy of Sciences10.21294/1814-4861-2018-17-4-14-23oncotomsk-810Research ArticleЛАБОРАТОРНЫЕ И ЭКСПЕРИМЕНТАЛЬНЫЕ ИССЛЕДОВАНИЯLABORATORY AND EXPERIMENTAL STUDIESИЗУЧЕНИЕ ОСОБЕННОСТЕЙ МИГРАЦИИ ДЕНДРИТНЫХ КЛЕТОК В ЭКСПЕРИМЕНТАЛЬНОЙ АНАЛИТИЧЕСКОЙ СИСТЕМЕ CELL-IQSTUDY OF DENDRITIC CELL MIGRATION USING CELL-IQ ANALYSIS SYSTEMhttps://orcid.org/0000-0002-7826-4861НехаеваТ. Л.NekhaevaT. L.

Россия, 197758, г. Санкт-Петербург, пос. Песочный, ул. Ленинградская, 68

кандидат медицинских наук, старший научный сотрудник научного отдела онкоиммунологии, ФГБУ «НМИЦ онкологии им. Н.Н. Петрова» Минздрава России

SPIN-код (РИНЦ): 5366-8969. Researcher ID (WOS): L-7268-2018. Author ID: 759111.

68, Leningradskaya Str., 197758-St.-Petersburg, Russia

MD, PhD, Researcher of N.N. Petrov Research Institute of Oncology, Department of Oncoimmunology

Researcher ID (WOS): L-7268-2018. Author ID: 759111

nehaevat151274@mail.ruhttps://orcid.org/0000-0003-4796-0386ДаниловаА. Б.DanilovaA. B.

Россия, 197758, г. Санкт-Петербург, пос. Песочный, ул. Ленинградская, 68

кандидат биологических наук, старший научный сотрудник научного отдела онкоиммунологии, ФГБУ «НМИЦ онкологии им. Н.Н. Петрова» Минздрава России

SPIN-код (РИНЦ): 9387-8328. Researcher ID (WOS): H-7828-2014. Author ID: 88221

68, Leningradskaya Str., 197758-St.-Petersburg, Russia

MD, PhD, Researcher of N.N. Petrov Research Institute of Oncology, Department of Oncoimmunology

Researcher ID (WOS): H-7828-2014. Author ID: 88221

 

anna_danilova@bk.ruhttps://orcid.org/0000-0002-7472-4613БалдуеваИ. А.BalduevaI. A.

Россия, 197758, г. Санкт-Петербург, пос. Песочный, ул. Ленинградская, 68

доктор медицинских наук, заведующая научным отделом онкоиммунологии ФГБУ «НМИЦ онкологии им. Н.Н. Петрова» Минздрава России 

SPIN-код (РИНЦ): 7512-8789. Researcher ID: H-9574-2014. Author ID: 268126

68, Leningradskaya Str., 197758-St.-Petersburg, Russia

MD, DSc, Head of Oncoimmunology Department, Leading Researcher of N.N. Petrov Research Institute of Oncology, Department of Oncoimmunology

Researcher ID: H-9574-2014. Author ID: 268126

biahome@mail.ruФГБУ «НМИЦ онкологии им. Н.Н. Петрова» Минздрава РоссииРоссияNational Medical Research Centre of Oncology named after N.N. Petrov, Ministry of Health of RussiaRussian Federation2018010920181741423Copyright © Нехаева Т.Л., Данилова А.Б., Балдуева И.А., 20182018Нехаева Т.Л., Данилова А.Б., Балдуева И.А.Nekhaeva T.L., Danilova A.B., Baldueva I.A.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.siboncoj.ru/jour/article/view/810

Дендритные клетки (ДК) – это специализированная группа антиген-презентирующих клеток с высокой функциональной пластичностью, которые проявляют иммуностимулирующий или иммуносупрессивный потенциал в зависимости от последовательности и комбинации стимулов  микроокружения, определяющих их дифференцировку, созревание, активацию. Разработка  противоопухолевых ДК-вакцин основана на способности ДК специфически активированных in vitro  мигрировать для презентации антигенов Т-лимфоцитам in vivo. В работе проведено изучение элементов  опухолевого микроокружения, способных оказывать влияние на миграцию ДК. Изучение подвижности ДК в  экспериментальной аналитической системе Cell-IQ показало наличие обратной корреляции высокой силы  между средней скоростью прохождения траектории ДК и содержанием иммуносупрессивных факторов (ИСФ)  в супернатантах культивируемых клеток меланомы кожи (TGFβ1, IL-10, IL-18, VEGF-A, EGF, FGF, HGF, sFASL  (p<0,01)). Была выявлена обратная зависимость высокой силы угла движения популяции ДК от экспрессии  раково-тестикулярных антигенов (РТА) и других опухолеассоциированных антигенов (ОАА) на опухолевых  клетках: Melan A, тирозиназы, семейств MAGE, BAGE, NY-ESO-1 (p<0,05). Скорость движения ДК в системе ко- культивирования с клетками меланомы №894 составила 30,10±2,23 мкм/ч и отличалась от таковой в  присутствии 1 нг/мл IL-10 (10,45±0,52 мкм/ч), 10 нг/мл TGFβ1 (14,32±0,42 мкм/ч), 50 нг/мл VEGF (18,7±1,89  мкм/ч) (p<0,05). Можно предполагать, что содержание этих ИСФ в периферической крови больных является  одним из факторов, определяющих клиническую эффективность противоопухолевой ДК-иммунотерапии.

Dendritic cells (DCs) belong to specialized pool of antigen-presenting cells with high functional plasticity and manifest with immunostimulatory or immunosuppressive potential  depending on sequence and combination of microenvironment stimuli, which determine their  differentiation, maturation and activation. The use of antitumor DCs vaccines is based  on the ability of DCs specifically activated in vitro migrate for antigen presentation to T- lymphocytes. We studied the components of the tumor microenvironment that are capable of inhibiting DCs migration. The study of the mobility of DCs in Cell-IQ experimental  analytical system showed the presence of an inverse correlation of high strength between  the average trajectory speed and the level  of immunosuppressive factors (ISFs) in  supernatants of cultured skin melanoma cells (TGFβ1, IL-10, IL-18, VEGF-A, EGF, FGF, HGF,  sFASL (p<0.01). An inverse relation of high force was found between the movement angle of the DCs population and the expression of cancer testis antigens (CTAs) and other tumor- associated antigens (TAAs) on tumor cells (Melan A, tyrosinase, families of MAGE, BAGE, NY- ESO-1 (p<0.01)). The speed of DCs movement in culture system with melanoma cells #894  was 30.10±2.23 μm/h and differed from that in the presence of IL-10 1 ng/ml (10.45±0.52  μm/h), TGFβ1 10 ng/ml (14.32±0.42 μm/h), VEGF 50 ng/ml (18.7±1.89 μm/h) (p<0.05).  One can assume that content of this ISFs in the blood is one of the factors determining clinical efficacy of DCs immune therapy.

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