mimmunМедицинская иммунологияMedical Immunology (Russia)1563-06252313-741XSPb RAACI10.15789/1563-0625-THO-3299mimmun-3299Research ArticleОРИГИНАЛЬНЫЕ СТАТЬИORIGINAL ARTICLESТранскриптомная гетерогенность моноцитов и её вклад в формирование иммунного микроокружения при раке предстательной железыTranscriptome heterogeneity of monocytes and its contribution to formation of immune microenvironment in prostate cancerhttps://orcid.org/0009-0000-8184-6072ШарифьяноваЮ. В.SharifyanovaYu. V.

Младший научный сотрудник, Лаборатория иммунологии. Институт урологии и клинической онкологии ФГБОУ ВО БГМУ Минздрава России, ученой степени,звания - нет

junior Researcher, academic degree, academic title – no

yuvsharifyanova@bashgmu.ruhttps://orcid.org/0000-0002-5995-2124ЕникееваК. И.EnikeevaK. I.

канд. фарм. наук; заведующий лабораторией иммунологии Института урологии и клинической онкологии ФГБОУ ВО БГМУ Минздрава России 

is the head of the laboratory; Institute of Urology and Clinical Oncology, Bashkir State Medical University; academic degree, academic title – Candidate of Pharmaceutical Sciences

kienikeeva@bashgmu.ruКоробейниковВ. Ю.KorobeynikovV. Yu.

младший научный сотрудник  лаборатории иммунологии Института урологии и клинической онкологии ФГБОУ ВО БГМУ Минздрава России, ученой степени,звания - нет

junior Researcher; Institute of Urology and Clinical Oncology, Bashkir State Medical University; Cancer Research Institute, Tomsk National Research Medical Center of the Russian Academy of Sciences; academic degree, academic title – no

wene28@mail.ruhttps://orcid.org/0009-0001-3298-3895ШмельковаП. Н.ShmelkovaP. N.

лаборант-исследователь лаборатории иммунологии Института урологии и клинической онкологии ФГБОУ ВО БГМУ Минздрава России, ученой степени,звания - нет

laboratory researcher: Institute of Urology and Clinical Oncology, Bashkir State Medical University; 5th year student of the Pediatric Faculty of the BSMU of the Ministry of Health of the Russian Federation

shmelkova_polina@mail.ruhttps://orcid.org/0009-0002-9174-4824ГайнуллинаМ. Х.GainullinаD. H.

лаборант-исследователь лаборатории иммунологии Института урологии и клинической онкологии ФГБОУ ВО БГМУ Минздрава России, ученой степени,звания - нет

laboratory researcher; Institute of Urology and Clinical Oncology, Bashkir State Medical University; 5th year student of the Pediatric Faculty of the BSMU of the Ministry of Health of the Russian Federation

gaynullina_d@inbox.ruhttps://orcid.org/0009-0000-1289-9365АкрамоваЭ. Р.AkramovaE. R.

младший научный сотрудник  лаборатории иммунологии Института урологии и клинической онкологии ФГБОУ ВО БГМУ Минздрава России, ученой степени,звания - нет

Junior Researcher: Institute of Urology and Clinical Oncology, Bashkir State Medical University; academic degree, academic title – no

erakramova@bashgmu.ruhttps://orcid.org/0000-0003-2125-4897ПавловВ. Н.PavlovV. N.

 Академик РАН, ректор ФГБОУ ВО БГМУ Минздрава России; ученая степень, ученое звание - доктор медицинских наук, профессор

Academician of the Russian Academy of Sciences, Rector of Bashkir State Medical University; academic degree, academic title - Doctor of Medical Sciences, Professor

erakramova@bashgmu.ruФГБОУ ВО БГМУ Минздрава России, Россия, УфаРоссияBashkir State Medical University, Ufa, Republic of Bashkortostan, RussiaRussian FederationФГБОУ ВО БГМУ Минздрава России, Россия, Уфа ; Научно-исследовательский институт онкологии ФГБНУ “Томский национальный исследовательский медицинский центр Российской академии наук”, Томск, РоссияRussian FederationBashkir State Medical University, Ufa, Republic of Bashkortostan, Russia; Research Institute of Oncology, Tomsk National Medical Research Center of Russian Academy of Sciences, Tomsk, RussiaRussian Federation20191111202500Online First3299Copyright © Шарифьянова Ю.В., Еникеева К.И., Коробейников В.Ю., Шмелькова П.Н., Гайнуллина М.Х., Акрамова Э.Р., Павлов В.Н., 20192019Шарифьянова Ю.В., Еникеева К.И., Коробейников В.Ю., Шмелькова П.Н., Гайнуллина М.Х., Акрамова Э.Р., Павлов В.Н.Sharifyanova Y.V., Enikeeva K.I., Korobeynikov V.Y., Shmelkova P.N., Gainullinа D.H., Akramova E.R., Pavlov V.N.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/3299

Наши современные знания о транскриптомных особенностях популяций моноцитов при раке простаты остаются весьма ограниченными. Это связано со сложностью исследования гетерогенных циркулирующих иммунных клеток, которая обусловлена изменчивостью клеточных фенотипов и антигенной экспрессией в опухоли. Применение секвенирования единичных клеток представляет возможность изучить транскрипционный профиль моноцитов, что может помочь ответить на многие вопросы, связанные с ролью различных субпопуляций моноцитов в формировании иммунного микроокружения опухоли у пациентов с раком простаты.

Целью исследования было охарактеризовать вклад транскриптомных особенностей субпопуляций моноцитов в формирование иммунного микроокружения при раке предстательной железы.

В исследование были включены 3 пациента с ацинарной аденокарциномой предстательной железы и 1 пациент с мелкоацинарной аденокарциномой предстательной железы. Транскриптомный профиль моноцитарных клеток периферической крови был получен с помощью секвенирования одноклеточной РНК (scRNA-seq). Подсчетные матрицы были получены с помощью Cell Ranger и проанализированы в R/Seurat с учетом дублетов (scDblFinder) и фильтрации низкокачественных клеток. После нормализации (SCTransform), интеграции (Harmony) и кластеризации (UMAP, PCA, FindClusters), кластеры аннотировали в Azimuth, а взаимодействия лиганд–рецептор исследовали с помощью CellChat.

Анализ транскриптомного профиля моноцитарных клеток с помощью секвенирования одноклеточной РНК (scRNA-seq) показал, что среди высокоэкспрессированных генов классических моноцитов прослеживается сеть, направленная на увеличение уровня провоспалительности иммуносреды (S100A8, S100A9, IL-6). Неклассические моноциты характеризовались повышением TRPC6, компонентами NO/cGMP‑сигналинга (GUCY1A1/B1) и Sema3A, ассоциированными с ангиогенезом, рекрутированием моноцитов и их поляризацией в иммуносупрессивные фенотипы. Промежуточные моноциты демонстрировали активацию регуляторно‑миграционных программ (ETS1, CCL5) вместе с элементами T‑клеточного взаимодействия (CD3E, CD247, SKAP1) и IL‑сигналинга. Сигнальные профили моноцитарных субпопуляций при раке простаты демонстрируют разнообразие как в исходящих, так и во входящих путях, отражая их функциональную неоднородность. Отмечаются особенности, связанные с активацией TGFβ-, галлектинового и TRAIL-сигналинга, что указывает на участие различных субтипов моноцитов в формировании межклеточных взаимодействий в опухолевом микроокружении.

Таким образом, проведенный анализ подчеркивает важную роль транскриптомных особенностей субпопуляций моноцитов в организации межклеточных взаимодействий и формировании иммунного микроокружения при раке простаты.

Our current knowledge on transcriptomic characteristics of monocytic populations in prostate cancer remains very limited. This is due to complexity of studying heterogeneous circulating immune cells, due to variability of cell phenotypes and antigen expression in malignant tumors. The use of single-cell sequencing provides an opportunity to study the transcriptional profile of monocytes, which may resolve many questions related to the role of different monocyte subpopulations in  formation of the tumor immune microenvironment in patients with prostate cancer. The aim of our study was to characterize the contribution of transcriptional features of monocyte subpopulations to the formation of the immune microenvironment in prostate cancer. Patients and methods: The study included 3 patients with acinar adenocarcinoma of the prostate and one patient with small acinar prostatic adenocarcinoma. The transcriptomic profile of peripheral blood monocyte cells was obtained using single-cell RNA sequencing (scRNA-seq). Counting matrices were obtained using Cell Ranger and analyzed in R/Seurat, taking into account duplicates (scDblFinder) and filtering low-quality cells. After normalization (SCTransform), integration (Harmony), and clustering (UMAP, PCA, FindClusters), clusters were annotated in Azimuth, and ligand–receptor interactions were explored using CellChat. Results: Transcriptome profiling of monocytic cells using single-cell RNA sequencing (scRNA-seq) revealed that among the highly expressed genes of classical monocytes, there is a network aimed at increasing the pro-inflammatory background of the immune environment (S100A8, S100A9, IL-6). Non-classical monocytes were characterized by increased expression of TRPC6, NO/cGMP signaling components (GUCY1A1/B1), and Sema3A, which are associated with angiogenesis, monocyte recruitment, and their polarization into immunosuppressive phenotypes. Intermediate monocytes demonstrated activation of regulatory-migratory programs (ETS1, CCL5) along with elements of T-cell interaction (CD3E, CD247, SKAP1) and IL signaling. The signaling profiles of monocyte subpopulations in prostate cancer show diversity in both outgoing and incoming pathways, reflecting their functional heterogeneity. Features associated with activation of TGFβ-, galectin-, and TRAIL-signaling are noted, thus suggesting involvement of different monocyte subtypes into arising intercellular interactions within tumor microenvironment. Hence, the performed analysis emphasizes an important role of transcriptional features of monocyte subpopulations in development of intercellular interactions and formation of the immune microenvironment in prostate cancer.

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