oncotomskСибирский онкологический журналSiberian journal of oncology1814-48612312-3168Tomsk National Research Medical Сепtеr of the Russian Academy of Sciences10.21294/1814-4861-2020-19-2-108-115oncotomsk-1406Research ArticleОБЗОРЫREVIEWSАбскопальный эффект радиотерапии и гипертермии: роль внеклеточных везикулAbscopal effect of radiotherapy and hyperthermia: role of exosomeshttps://orcid.org/0000-0003-4595-4177ЮнусоваН. В.YunusovaN. V.

Юнусова Наталья Валерьевна - ведущий научный сотрудник лаборатории биохимии опухолей, НИИО ТНИМЦ РАН, ResearcherID (WOS): C-9275-2012. Author ID (Scopus): 8354141400.

Томск, 634009, пер. Кооперативный, 5; Томск, 634050, Московский тракт, 2

Natalia V. Yunusova - DSc, Leading Researcher, Laboratory of Tumor Biochemistry, Cancer Research Institute, TNR MC, Researcher ID (WOS): C-9275-2012. Author ID (Scopus): 8354141400.

5, Kooperativny str., 634009, Tomsk; 2, Moskovsky trakt, 634050, Tomsk

Bochkarevanv@oncology.tomsk.ruhttps://orcid.org/0000-0002-7703-9734ФедоровА. А.FedorovA. A.

Федоров Александр Александрович - научный сотрудник отделения общей онкологии, Научно-исследовательский институт онкологии, Researcher ID (WOS): R-5727-2017.

Томск, 634009, пер. Кооперативный, 5

Alexandr A. Fyedorov - MD, Researcher, General Oncology Department, Researcher ID (WOS): R-5727-2017.

5, Kooperativny str., 634009, Tomsk

https://orcid.org/0000-0002-4345-7719СтарцеваЖ. А.StartsevaZh. A.

Старцева Жанна Александровна - заведующая отделением лучевой терапии, Научно-исследовательский институт онкологии, ResearcherID (WOS): E-1286-2012. AuthorID (Scopus): 57188995294.

Томск, 634009, пер. Кооперативный, 5

Zhanna A. Startseva - MD, Head of Radiation Therapy Department, Cancer Research Institute, Researcher ID (WOS): E-1286-2012. Author ID (Scopus): 57188995294.

5, Kooperativny str., 634009, Tomsk

YeonJ. H.YeonJ. H.

Ju Hun Yeon - Center for BioMicrosystems, Brain Science Institute, KIST; Department of Integrative Biosciences, UBE.

5. Hwarang-ro 14-gil, Seongbuk-gu, Seoul 02792; Cheonan, 31228

Ju Hun Yeon - Center for BioMicrosystems, Brain Science Institute, KIST; Department of Integrative Biosciences, UBE.

5. Hwarang-ro 14-gil, Seongbuk-gu, Seoul 02792; Cheonan, 31228

Научно-исследовательский институт онкологии, Томский национальный исследовательский медицинский центр, Российская академия наук; Сибирский государственный медицинский университетРоссияCancer Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences; Siberian State Medical UniversityRussian FederationНаучно-исследовательский институт онкологии, Томский национальный исследовательский медицинский центр, Российская академия наукРоссияCancer Research Institute, Tomsk National Research Medical Center, Russian Academy of SciencesRussian FederationCenter for BioMicrosystems, Brain science Institute, Korea Institute of science and technology (KIsT); Department of Integrative Biosciences, University of Brain EducationРоссияCenter for BioMicrosystems, Brain science Institute, Korea Institute of science and technology (KIsT); Department of Integrative Biosciences, University of Brain EducationRussian Federation202029042020192108115Copyright © Юнусова Н.В., Федоров А.А., Старцева Ж.А., Yeon J.H., 20202020Юнусова Н.В., Федоров А.А., Старцева Ж.А., Yeon J.H.Yunusova N.V., Fedorov A.A., Startseva Z.A., Yeon J.H.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.siboncoj.ru/jour/article/view/1406

В обзоре представлены обобщенные данные о роли ионизирующего излучения/гипертермии как модулирующих факторов в секреции/составе экзосом. Опухолевые экзосомы являются важными участниками формирования микроокружения опухоли путем модуляции воспалительного ответа в опухоли, влияния на дифференцировку фибробластов и мезенхимных клеток в миофибробласты, запуска ангиогенного процесса, стимулирования эпителиально-мезенхимальной трансформации и формирования опухолевых прениш. Описаны некоторые механизмы поведения опухолевых клеток-реципиентов, получающих экзосомы от облученных клеток, включая активацию передачи сигналов Akt, стабилизацию MMP9/MMP2, усиление опосредованной экзосомами подвижности. Модели invitro продемонстрировали эффективность экзосом из мезенхимальных стволовых клеток (МСК) для модуляции как прямого воздействия радиации/гипертермии, так и усиления абскопального эффекта. Экзосомы, полученные из MsC, являются наиболее привлекательным носителем для доставки белков, микроРНК, лекарств, металлов к опухолевым клеткам реципиента. Экзосомы MsC усиливают эффекты как лучевой терапии, так и гипертермии в экспериментальных исследованиях. Тем не менее остается ряд важных вопросов, касающихся: а) наиболее эффективных вариантов введения экзосом MsC для модуляции лучевой терапии/гипертермии; б) дозы ионизирующего излучения; в) вариантов гипертермии; г) детальных механизмов воздействия экзосом из облученных МСК на опухолевые клетки и микроокружение опухоли.

The review presents data on the role of ionizing radiation/hyperthermia as modulating factors in exosome secretion/composition. Tumor-derived exosomes are important participants in the formation of the tumor microenvironment. They modulate the inflammatory response in the tumor, influence the capability of fibroblasts and mesenchymal cells to differentiate into myofibroblasts, trigger the angiogenic process, promote epithelial to mesenchymal transformation of tumor cells and form the pre-metastatic nisches. The review describes the mechanisms of behavior of the recipient tumor cells receiving exosomes from irradiated cells, including activation of akt signaling, stabilization of MMP9/MMP2, and enhancement of exosome-mediated motility. In vitro models demonstrate the efficacy of exosomes from mesenchymal stem cells (MsC) to modulate both direct and abscopal effects of radiation therapy/hyperthermia. Exosomes derived from MsC are the most attractive carriers for the delivery of proteins, miRNAs, drugs, and metals to the recipient tumor cells. MsC-derived exosomes potentiate the efficacy of both radiotherapy and hyperthermia in vitro studies. However, some important aspects regarding a)             the most effective options for administering MsC/MsC exosomes to modulate radiotherapy/hyperthermia; b) radiation dose; c) options of hyperthermia; d) detailed mechanisms of the effect of irradiated MsC-derived exosomes on the tumor microenvironment and cancer cells, still remain poorly understood.

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