mimmunМедицинская иммунологияMedical Immunology (Russia)1563-06252313-741XSPb RAACI10.15789/1563-0625-ROC-2512mimmun-2512Research ArticleОБЗОРЫREVIEWSРоль цитокинов при гепатоцеллюлярной карциномеRole of cytokines in hepatocellular carcinomahttps://orcid.org/0000-0003-2208-9918АгаевТ.AghayevT.

Агаев Туран Ага Ровшан оглы, соискатель ученой степени кафедры иммунологии МБФ

117997, Москва, ул. Островитянова, 1Тел.: 8 (977) 488-93-94

Aghayev Turan Aga Rovshan Ogly, Postgraduate Student, Department of Immunology

117997, Moscow, Ostrovitianov str., 1Phone: 7 (977) 488-93-94

turan_aghayev@yahoo.comhttps://orcid.org/0000-0003-0635-1082ТитеринаЕ. К.TiterinaE. K.

сотрудник научно-исследовательской лаборатории молекулярной фармакологии, Научно-исследовательский институт трансляционной медицины

Москва

Research Associate, Laboratory of Molecular Pharmacology, Institute for Translational Medicine

Moscow

lizatiterina@gmail.comhttps://orcid.org/0000-0002-6224-2510ХореваМ. В.KhorevaM. V.

д.м.н., доцент, профессор кафедры иммунологии МБФ

Москва

PhD, MD (Medicine), Associate Professor, Professor, Department of Immunology

Moscow

markhoreva@yandex.ruhttps://orcid.org/0000-0003-1271-3078ГанковскаяЛ. В.GankovskayaL. V.

д.м.н., профессор кафедры иммунологии МБФ

Москва

PhD, MD (Medicine), Professor, Department of Immunology

Moscow

lvgan@yandex.ruФГАОУ ВО «Российский национальный исследовательский медицинский университет имени Н.И. Пирогова» Министерства здравоохранения РФРоссияN. Pirogov Russian National Research Medical UniversityRussian Federation202231102022245889902Copyright © Агаев Т., Титерина Е.К., Хорева М.В., Ганковская Л.В., 20222022Агаев Т., Титерина Е.К., Хорева М.В., Ганковская Л.В.Aghayev T., Titerina E.K., Khoreva M.V., Gankovskaya L.V.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/2512

Рак печени занимает пятое место в мире среди всех видов рака и третье место среди смертей, связанных с раковыми заболеваниями. Гепатоцеллюлярная карцинома (ГЦК) является первичной, не включающей метастазы в печень из других участков и самой распространенной формой рака печени и одной из ведущей причиной смерти от рака во всем мире. ГЦК включает генетически и морфологически гетерогенную группу злокачественных опухолей. ГЦК характеризуется гендерной предрасположенностью: она встречается у мужчин в 1,5 чаще, чем у женщин. Вирусные инфекции, такие как гепатит В и С, являются основными факторами риска развития ГЦК, но также в развитых странах неалкогольный стеатогепатит (НАСГ), связанный с метаболическим синдромом и сахарным диабетом второго типа, становится все более часто встречаемым фактором риска развития заболевания. Механизмы, лежащие в основе развития ГЦК, основываются на генетических изменениях опухолевых клеток и их микроокружения. В последнее время роль изменений в микроокружении опухоли привлекает большее внимание и становится ключевой характеристикой в патогенезе ГЦК на всех стадиях злокачественного процесса. Гепатоциты имеют тесную связь с иммунными клетками, так как в печени помимо гепатоцитов присутствуют клетки Купфера, клетки миелоидного ряда (дендритные клетки, моноциты и нейтрофилы) и другие типы клеток (Т- и В-лимфоциты, NK и NKT и т. д.). Выделяемые различными иммунными клетками печени цитокины оказывают влияние на процессы в печени, такие как развитие воспаления и рака. Хроническое воспаление возникает в результате постоянных стимулов или недостатков в механизмах разрешения воспаления. Его ключевые особенности включают инфильтрацию иммунных клеток, наличие медиаторов воспаления и дисбаланс про- и противовоспалительных цитокинов, приводящих к возникновению агрессивного ангиогенеза и ремоделирования тканей, что в свою очередь приводит к озлокачествлению процесса. На данный момент существуют несколько подходов в лечении ГЦК в зависимости от стадии заболевания. Иммунотерапия и ее комбинации показали положительную динамику, и дальнейшие исследования в этой области помогут в борьбе на терминальных стадиях ГЦК. Разнообразные цитокины и их функции в развитии ГЦК являются предметом настоящего обзора.

Liver cancer ranks No. 5 in the world among all types of cancer and takes 3rd position among cancer-related deaths. Hepatocellular carcinoma (HCC) is a primary malignancy which does not include liver metastases from other sites. It is the most common form of liver cancers, and one of the leading causes of cancer-related deaths worldwide. HCC includes genetically and morphologically heterogeneous group of malignant tumors. HCC is characterized by a gender predisposition, namely, it occurs in men 1.5-fold more often, than in women. Viral infections such as hepatitis B and C are major risk factors for HCC. Moreover, non-alcoholic steatohepatitis (NASH) associated with metabolic syndrome and type 2 diabetes also becomes an increasingly common risk factor in developed countries. The mechanisms underlying the development of HCC are based on genetic changes in tumor cells and their microenvironment. Recently, the role of changes in the tumor microenvironment has drawn more attention, thus becoming the key characteristic in the HCC pathogenesis at all stages of the malignant process. Hepatocytes have a close relationship with immune cells, since in the liver, in addition to hepatocytes, there are Kupffer cells, myeloid cells (dendritic cells, monocytes and neutrophils) and other types of immune cells (T and B lymphocytes, NK and NKT, etc.). Cytokines released by various immune cells in the liver may influence liver processes, e.g., inflammation and carcinogenesis. Chronic inflammation results from persistent stimulation, or deficiencies of anti-inflammatory mechanisms. Its key features include immune cell infiltration, presence of inflammatory mediators, and imbalance of pro- and antiinflammatory cytokines leading to aggressive angiogenesis and tissue remodeling which, in turn, promotes the malignant process. Currently, there are several approaches to the HCC treatment which depend on the stage of the disease. Immunotherapy and its combinations have shown positive advances, and further research in this area will provide therapeutic options at the terminal stages of HCC. A variety of cytokines and their functions in HCC development are discussed in the present review article.

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