cancerspЮжно-Российский онкологический журнал/ South Russian Journal of CancerSouth Russian Journal of Cancer2686-9039АНО "Перспективы онкологии"10.37748/2686-9039-2023-4-3-7TXUMANcancersp-208Research ArticleОбзорREVIEWИммунотерапия эпителиальных опухолей вилочковой железыImmunotherapy for epithelial tumors of the thymushttps://orcid.org/0000-0003-3061-6108КитО. И.KitO. I.

 

Кит Олег Иванович – академик РАН, д.м.н., профессор, генеральный директор, ФГБУ «НМИЦ онкологии» Минздрава России, г. Ростов-на-Дону, Российская Федерация.

ORCID: https://orcid.org/0000-0003-3061-6108, SPIN: 1728-0329, AuthorID: 343182, ResearcherID: U-2241-2017, Scopus Author ID: 55994103100

 

Oleg I. Kit – Academician at the Russian Academy of Sciences, Dr. Sci. (Med.), professor, general director, National Medical Research Centre for Oncology, Rostov-on-Don, Russian Federation.

ORCID: https://orcid.org/0000-0003-3061-6108, SPIN: 1728-0329, AuthorID: 343182, ResearcherID: U-2241-2017, Scopus Author ID: 55994103100

rnioi@list.ruhttps://orcid.org/0000-0003-0640-2994ХарагезовД. А.KharagezovD. A.

 

Харагезов Дмитрий Акимович – к.м.н., онколог, хирург, заведующий отделением торакальной онкологии, ФГБУ «НМИЦ онкологии» Минздрава России, г. Ростов-на-Дону, Российская Федерация.

ORCID: https://orcid.org/0000-0003-0640-2994, SPIN: 5120-0561, AuthorID: 733789, ResearcherID: AAZ-3638-2021, Scopus Author ID: 56626499300

 

Dmitriy A. Kharagezov – Cand. Sci. (Med.), oncologist, surgeon, head of the department of thoracic oncology, National Medical Research Centre for Oncology, Rostov-on-Don, Russian Federation.

ORCID: https://orcid.org/0000-0003-0640-2994, SPIN: 5120-0561, AuthorID: 733789, ResearcherID: AAZ-3638-2021, Scopus Author ID: 56626499300

dmitr8@mail.ruhttps://orcid.org/0000-0002-6655-7632ЛазутинЮ. Н.LazutinYu. N.

 

Лазутин Юрий Николаевич – к.м.н., доцент, ведущий научный сотрудник отдела торакоабдоминальной онкологии, ФГБУ «НМИЦ онкологии» Минздрава России, г. Ростов-на-Дону, Российская Федерация.

ORCID: https://orcid.org/0000-0002-6655-7632, SPIN: 5098-7887, AuthorID: 364457

 

Yuriy N. Lazutin – Cand. Sci. (Med.), associate professor, leading researcher of the department of thoracic surgery, National Medical Research Centre for Oncology, Rostov-on-Don, Russian Federation.

ORCID: https://orcid.org/0000-0002-6655-7632, SPIN: 5098-7887, AuthorID: 364457

ellada.mirzoyan@yandex.ruhttps://orcid.org/0000-0002-0328-9714МирзоянЭ. А.MirzoyanE. A.

 

Мирзоян Эллада Арменовна – аспирант, ФГБУ «НМИЦ онкологии» Минздрава России, г. Ростов-на-Дону, Российская Федерация.

ORCID: https://orcid.org/0000-0002-0328-9714, SPIN: 2506-8605, AuthorID: 1002948, ResearcherID: AAZ-2780-2021, Scopus Author ID: 57221118516

 

Ellada A. Mirzoyan – PhD student, National Medical Research Centre of Oncology, Rostov-on-Don, Russian Federation.

ORCID: https://orcid.org/0000-0002-0328-9714, SPIN: 2506-8605, AuthorID: 1002948, ResearcherID: AAZ-2780-2021, Scopus Author ID: 57221118516

ellada.mirzoyan@yandex.ruhttps://orcid.org/0000-0002-2589-7606МилакинА. Г.MilakinA. G.

 

Милакин Антон Григорьевич – онколог отделения торакальной онкологии, ФГБУ «НМИЦ онкологии» Минздрава России, г. Ростов-на-Дону, Российская Федерация.

ORCID: https://orcid.org/0000-0002-2589-7606, SPIN: 7737-4737, AuthorID: 794734

 

Anton G. Milakin – MD, oncologist, department of thoracic oncology, National Medical Research Centre for Oncology, Rostov-on-Don, Russian Federation.

ORCID: https://orcid.org/0000-0002-2589-7606, SPIN: 7737-4737, AuthorID: 794734

ellada.mirzoyan@yandex.ruhttps://orcid.org/0000-0003-4513-7548СтатешныйО. Н.StateshnyO. N.

 

Статешный Олег Николаевич – онколог отделения торакальной онкологии, ФГБУ «НМИЦ онкологии» Минздрава России, г. Ростов-на-Дону, Российская Федерация.

ORCID: https://orcid.org/0000-0003-4513-7548, SPIN: 9917-1975, AuthorID: 1067071

 

Oleg N. Stateshny – MD, oncologist, department of thoracic oncology, National Medical Research Centre for Oncology, Rostov-on-Don, Russian Federation.

ORCID: https://orcid.org/0000-0003-4513-7548, SPIN: 9917-1975, AuthorID: 1067071

ellada.mirzoyan@yandex.ruАйрапетоваТ. Г.AyrapetovaT. G.

 

Айрапетова Тамара Георгиевна – к.м.н., хирург отделения торакальной онкологии, ФГБУ «НМИЦ онкологии» Минздрава России, г. Ростов-на-Дону, Российская Федерация.

SPIN: 8121-4039, AuthorID: 794672

 

Tamara G. Ayrapetova – Cand. Sci. (Med.), surgeon of the department of thoracic oncology, National Medical Research Centre for Oncology, Rostov-on-Don, Russian Federation.

SPIN: 8121-4039, AuthorID: 794672

ellada.mirzoyan@yandex.ruhttps://orcid.org/0000-0003-2572-1624ЛейманИ. А.LeymanI. A.

 

Лейман Игорь Александрович – к.м.н., врач-онколог отделения торакальной хирургии, ФГБУ «НМИЦ онкологии» Минздрава России, г. Ростов-на-Дону, Российская Федерация.

ORCID: https://orcid.org/0000-0003-2572-1624, SPIN: 2551-0999, AuthorID: 735699

 

Igor A. Leyman – Cand. Sci. (Med.), MD, oncologist, department of thoracic oncology, National Medical Research Centre for Oncology, Rostov-on-Don, Russian Federation.

ORCID: https://orcid.org/0000-0003-2572-1624, SPIN: 2551-0999, AuthorID: 735699

ellada.mirzoyan@yandex.ruhttps://orcid.org/0000-0003-0783-8626ГаппоеваМ. А.GappoevaM. A.

 

Гаппоева Мадина Асланбековна – онколог клинико-диагностического отделения, ФГБУ «НМИЦ онкологии» Минздрава России, г. Ростов-на-Дону, Российская Федерация.

ORCID: https://orcid.org/0000-0003-0783-8626

 

Madina A. Gappoeva – oncologist of the clinical and diagnostic department, National Medical Research Centre for Oncology, Rostov-on-Don, Russian Federation.

ORCID: https://orcid.org/0000-0003-0783-8626

ellada.mirzoyan@yandex.ruhttps://orcid.org/0000-0002-9603-1607ВитковскаяВ. Н.VitkovskayaV. N.

 

Витковская Виктория Николаевна – онколог клинико-диагностического отделения, ФГБУ «НМИЦ онкологии» Минздрава России, г. Ростов-на-Дону, Российская Федерация.

ORCID: https://orcid.org/0000-0002-9603-1607

 

Viktoriia N. Vitkovskaya – oncologist of the clinical and diagnostic department, National Medical Research Centre for Oncology, Rostov-on-Don, Russian Federation.

ORCID: https://orcid.org/0000-0002-9603-1607

ellada.mirzoyan@yandex.ruhttps://orcid.org/0000-0002-5351-3251ИозефиК. Д.IozefiK. D.

 

Иозефи Кристиан Дмитриевич – аспирант, ФГБУ «НМИЦ онкологии» Минздрава России, г. Ростов-на-Дону, Российская Федерация.

ORCID: https://orcid.org/0000-0002-5351-3251, SPIN: 1232-3097, AuthorID: 1122592, ResearcherID: AAZ-3632-2021

 

Kristian D. Iozefi – PhD student, National Medical Research Centre for Oncology, Rostov-on-Don, Russian Federation. 

ORCID: https://orcid.org/0000-0002-5351-3251, SPIN: 1232-3097, AuthorID: 1122592, ResearcherID: AAZ-3632-2021

ellada.mirzoyan@yandex.ruhttps://orcid.org/0000-0003-0645-0937ХомидовМ. А.KhomidovM. A.

 

Хомидов Мехруллоходжа Абдусудурович – аспирант, ФГБУ «НМИЦ онкологии» Минздрава России, г. Ростов-на-Дону, Российская Федерация.

ORCID: https://orcid.org/0000-0003-0645-0937

 

Mehrullohodja A. Khomidov – PhD student, National Medical Research Centre for Oncology, Rostov-on-Don, Russian Federation.

ORCID: https://orcid.org/0000-0003-0645-0937 

ellada.mirzoyan@yandex.ruФГБУ «НМИЦ онкологии» Минздрава РоссииРоссияNational Medical Research Centre for OncologyRussian Federation202307082023435667Copyright © Кит О.И., Харагезов Д.А., Лазутин Ю.Н., Мирзоян Э.А., Милакин А.Г., Статешный О.Н., Айрапетова Т.Г., Лейман И.А., Гаппоева М.А., Витковская В.Н., Иозефи К.Д., Хомидов М.А., 20232023Кит О.И., Харагезов Д.А., Лазутин Ю.Н., Мирзоян Э.А., Милакин А.Г., Статешный О.Н., Айрапетова Т.Г., Лейман И.А., Гаппоева М.А., Витковская В.Н., Иозефи К.Д., Хомидов М.А.Kit O.I., Kharagezov D.A., Lazutin Y.N., Mirzoyan E.A., Milakin A.G., Stateshny O.N., Ayrapetova T.G., Leyman I.A., Gappoeva M.A., Vitkovskaya V.N., Iozefi K.D., Khomidov M.A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.cancersp.com/jour/article/view/208

Тимомы и карциномы вилочковой железы, также известные как эпителиальные опухоли тимуса (ОТ), являются редкими злокачественными новообразованиями, но также наиболее частыми солидными опухолями переднего средостения. Заболеваемость не превышает 1,3–1,7 на миллион жителей в год. В Европе ежегодно регистрируется около 1500 новых случаев, а средний возраст заболевших составляет от 40 до 50 лет.

Происходя из эпителиального компонента тимуса – первичного лимфоидного органа, они из-за своей уникальной биологии сопровождаются высоким риском развития аутоиммунных расстройств. Действительно, до 30 % больных ОТ страдают аутоиммунными расстройствами (AИР), наиболее частым из которых является миастения гравис (MГ). AИР выявляются не только при диагностике опухоли, но и во время последующего наблюдения. За редким исключением в ОТ отсутствуют специфические мишени для таргетной терапии. Ингибиторы иммунных контрольных точек (ИИКТ) подавляют способность опухолевых клеток уклоняться от иммунного надзора, усиливая их киллинг. Беспрецедентные достижения иммунотерапии (ИТ) в лечении метастатического немелкоклеточного рака легкого (НМРЛ) и меланомы сделали обоснованным изучение эффективности назначения ИИКТ пациентам с ОТ. Распространенность АИР при разных морфологических подтипах ОT может повлиять на решение о проведении ИТ из-за повышенного риска токсичности. В обзоре обобщены современные данные об эффективности ИТ при тимоме и раке тимуса (РT) и обсуждаются несколько нерешенных проблем, связанных с использованием ИИКТ при ОТ.

Цель данного обзора – представить современные данные по обсуждаемому вопросу и возможные прогностические биомаркеры для ИТ и осветить проблемы, связанные с аутоиммунными расстройствами (АИР).

По нашему мнению, глубокое понимание молекулярно-генетического и иммунного ландшафта эпителиальных опухолей вилочковой железы и взаимодействия ИИКТ с иммунной системой является ключом к повышению эффективности и предотвращению побочного аутоиммунного действия ИТ. Всестороннее решение существующих проблем, несомненно, позволит открыть новые возможности лекарственного лечения этого редкого и трудного заболевания.

Thymomas and carcinomas of the thymus gland, also known as epithelial tumors of the thymus (TT) are rare malignant neoplasms, but are the most common solid tumors of the anterior mediastinum. The incidence does not exceed 1.3–1.7 per million inhabitants per year. In Europe, about 1,500 new cases are registered annually, and the average age of patients is around 40–50 years.

Originating from the epithelial component of the thymus, the primary lymphoid organ, they are accompanied by a high risk of developing autoimmune disorders due to their unique biology. Indeed, up to 30 % of TETS patients suffer from autoimmune disorders (AID), the most common of which is myasthenia gravis (MG). AID are detected not only during the diagnosis of a tumor, but also during follow-up. With rare exceptions, there are no specific targets for targeted therapy in TETS. Immune checkpoint inhibitors (ICIs) halt the ability of tumor cells to evade immune surveillance, enhancing their killing. Unprecedented achievements of immunotherapy (IT) in the treatment of metastatic non-small cell lung cancer (NSCLC) and melanoma have made it reasonable to study the effectiveness of prescribing ICI in patients with TETs. The prevalence of AIR in different morphological subtypes of TETs may influence the decision to conduct IT due to the increased risk of toxicity. The review summarizes current data on the effectiveness of IT in thymoma and thymus cancer (TC) and discusses several unresolved problems associated with the use of ICI in TETs.

The purpose of this review is to present up-to-date data on the issue under discussion and possible prognostic biomarkers for IT, and to highlight the problems associated with autoimmune disorders (AID). In our opinion, a deep understanding of the molecular genetic and immune landscape of thymus epithelial tumors and the interaction of ICI with the immune system is the key to improving the effectiveness and preventing the side effects of autoimmune IT. A comprehensive solution to existing problems will undoubtedly open up new possibilities for the drug treatment of this rare and difficult disease.

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