akusherstvoObstetrics, Gynecology and ReproductionАкушерство, Гинекология и Репродукция2313-73472500-3194IRBIS LLC10.17749/2313-7347/ob.gyn.rep.2025.647akusherstvo-2483Research ArticleREVIEW ARTICLEНАУЧНЫЙ ОБЗОРTIGIT immunosuppressive role in female reproductive system malignant neoplasms: from mechanism to therapyИммуносупрессивная роль TIGIT в опухолях женской репродуктивной системы: от механизма к терапииhttps://orcid.org/0009-0004-2111-467XХамадьяноваА. У.KhamadyanovaA. U.

Хамадьянова Аида Ульфатовна, к.м.н.

450008 Уфа, ул. Ленина, д. 3

Aida U. Khamadyanova, MD, PhD

3 Lenin Str., Ufa 450008

aida.khamadyanova@mail.ruhttps://orcid.org/0009-0008-7480-9642РомановаА. И.RomanovaA. I.

Романова Александра Игоревна

127006 Москва, Долгоруковская ул., д. 4

Aleksandra I. Romanova

4 Dolgorukovskaya Str., Moscow 127006

https://orcid.org/0009-0000-8588-7701СклярА. Н.SklyarA. N.

Скляр Александр Николаевич

153012 Иваново, Шереметевский проспект, д. 8

Aleksandr N. Sklyar

8 Sheremetevsky Avenue, Ivanovo 153012

https://orcid.org/0009-0007-5415-3706ЯмиловаА. П.YamilovaA. P.

Ямилова Аделина Петровна

620028 Екатеринбург, ул. Репина, д. 3

Adelina P. Yamilova

3 Repin Str., Еkaterinburg 620028

https://orcid.org/0009-0001-3171-0561Миранда ПланасМ. Г.Miranda PlanasM. G.

Миранда Планас Марина Геннадиевна

287501, Донецкая народная республика, Мариуполь, проспект Ленина, д. 80

Marina G. Miranda Planas, MD

80 Lenin Avenue, Mariupol, Donetsk People's Republic 287501

https://orcid.org/0009-0007-6521-894XГалееваГ. Д.GaleevaG. D.

Галеева Гузель Димовна

450008 Уфа, ул. Ленина, д. 3

Guzel D. Galeeva

3 Lenin Str., Ufa 450008

https://orcid.org/0009-0004-5109-9757ХакимовС. Р.KhakimovS. R.

Хакимов Салават Рафаилович

450008 Уфа, ул. Ленина, д. 3

 

Salavat R. Khakimov

3 Lenin Str., Ufa 450008

https://orcid.org/0009-0008-9166-0552ЯкубовА. А.YakubovA. A.

Якубов Абдуманон Абдулмуминович

734003 Душанбе, проспект Рудаки, д. 139

Abdumanon A. Yakubov

139 Rudaki Avenue, Dushanbe 734003, Republic of Tajikistan

https://orcid.org/0009-0001-1500-3154БикиняевС. К.BikinyaevS. K.

Бикиняев Салават Калбаевич

625039 Тюмень, ул. Мельникайте, д. 75

Salavat K. Bikinyaev, MD

75 Melnikaite Str., Tyumen 625039

https://orcid.org/0009-0003-7784-851XМаммаевШ. М.MammaevSh. M.

Маммаев Шапаудин Магомедович

344022 Ростов-на-Дону, Нахичеванский пер., 29

Shapaudin M. Mammaev

29 Nakhichevansky Lane, 29 Rostov-on-Don 344022 

https://orcid.org/0009-0003-1900-7587ВарданянА. А.VardanyanA. A.

Варданян Анастасия Андреевна

344022 Ростов-на-Дону, Нахичеванский пер., 29

Anastasia A. Vardanyan

29 Nakhichevansky Lane, 29 Rostov-on-Don 344022 

https://orcid.org/0009-0002-1942-7349КантаеваП. А.KantaevaP. A.

Кантаева Петимат Ахмедовна

364034 Грозный, ул. А. Шерипова, д. 32

Petimat A. Kantaeva

32 A. Sheripov Str., Grozny 364034 

https://orcid.org/0009-0003-6595-3865АлгириеваТ. Р.AlgirievaT. R.

Алгириева Танзила Ризвановна

117198 Москва, ул. Миклухо-Маклая, д. 6

Tanzila R. Algirieva

6 Miklukho-Maklaya Str., Moscow 117198

ФГБОУ ВО «Башкирский государственный медицинский университет» Министерства здравоохранения Российской ФедерацииРоссияBashkir State Medical University, Ministry of Health of the Russian FederationRussian FederationФГБОУ ВО «Российский университет медицины» Министерства здравоохранения Российской ФедерацииРоссияRussian University of Medicine, Ministry of Health of the Russian FederationRussian FederationФГБОУ ВО «Ивановский государственный медицинский университет» Министерства здравоохранения Российской ФедерацииРоссияIvanovo State Medical University, Ministry of Health of the Russian FederationRussian FederationФГБОУ ВО «Уральский государственный медицинский университет» Министерства здравоохранения Российской ФедерацииРоссияUral State Medical University, Ministry of Health of the Russian FederationRussian FederationГБУ ДНР «Центр первичной медико-санитарной помощи» № 3 г. МариуполяРоссияPrimary Health Care Center No. 3Russian FederationТаджикский государственный медицинский университет имени Абуали ибни СиноТаджикистанAvicenna Tajik State Medical UniversityTajikistanГБУЗ ТО «Областная клиническая больница № 2»РоссияRegional Clinical Hospital No. 2Russian FederationФГБОУ ВО «Ростовский государственный медицинский университет» Министерства здравоохранения Российской ФедерацииРоссияRostov State Medical University, Ministry of Health of the Russian FederationRussian FederationФГБОУ ВО «Чеченский государственный университет имени А.А. Кадырова»РоссияKadyrov Chechen State UniversityRussian FederationФГАОУ ВО «Российский университет дружбы народов имени Патриса Лумумбы»РоссияPatrice Lumumba Peoples' Friendship University of RussiaRussian Federation20203006202500Online First2483Copyright © Khamadyanova A.U., Romanova A.I., Sklyar A.N., Yamilova A.P., Miranda Planas M.G., Galeeva G.D., Khakimov S.R., Yakubov A.A., Bikinyaev S.K., Mammaev S.M., Vardanyan A.A., Kantaeva P.A., Algirieva T.R., 20202020Хамадьянова А.У., Романова А.И., Скляр А.Н., Ямилова А.П., Миранда Планас М.Г., Галеева Г.Д., Хакимов С.Р., Якубов А.А., Бикиняев С.К., Маммаев Ш.М., Варданян А.А., Кантаева П.А., Алгириева Т.Р.Khamadyanova A.U., Romanova A.I., Sklyar A.N., Yamilova A.P., Miranda Planas M.G., Galeeva G.D., Khakimov S.R., Yakubov A.A., Bikinyaev S.K., Mammaev S.M., Vardanyan A.A., Kantaeva P.A., Algirieva T.R.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.gynecology.su/jour/article/view/2483Introduction

Introduction. Malignant neoplasms of the female reproductive system (ovarian, endometrial, and cervical cancers) account for a significant proportion of female oncology morbidity and mortality. Standard treatment methods, including surgery, chemotherapy, and radiotherapy, show limited efficacy in recurrent and drug-resistant tumors. The development of immunotherapy, particularly immune checkpoint inhibitors (ICI), has opened new therapeutic avenues; however, their clinical effectiveness in gynecologic oncology remains suboptimal. In connection with this, it has increased an interest in novel targets, notably TIGIT (T-cell immunoglobulin and ITIM domain), a co-inhibitory receptor expressed on T-cells and natural killer cells (NK-cells), which plays a key role in establishing an immunosuppressive tumor microenvironment.

Aim

Aim: to systematize current data on the biological function of TIGIT and relevant ligands, its role in immunosuppression in malignant neoplasms of the female reproductive system as well as evaluate a therapeutic potential of its blockade during a personalized immunotherapy.

Materials and Methods

Materials and Methods. This review was conducted according to the PRISMA methodology. There was performed a systematic literature search for publications from 2013 to 2024 in the databases PubMed/MEDLINE, Scopus, Web of Science, Embase, Google Scholar, and ClinicalTrials.gov. A total of 91 scientific sources and 7 registered clinical trials were included. Original studies, meta-analyses, reviews, guidelines, and clinical trial reports were analyzed.

Results

Results. TIGIT interacts with several ligands (CD155, CD112, Nectin-4, Fap2), leading to suppression of NK-cells and CD8+ T-cells activity, macrophage polarization toward M2 phenotype, activation of regulatory T-cells (Treg), and impaired antigen presentation. TIGIT is co-expressed with PD-1 (programmed cell death protein 1) and CD96, forming a suppressive signaling network. Its elevated expression is associated with disease progression in ovarian, endometrial, and cervical cancers, reduced cytotoxicity of tumor-infiltrating lymphocytes (TIL), and poor prognosis. TIGIT blockade, especially in combination with PD-1/PD-L1 (programmed cell death ligand 1), restores effector cell function and enhances antitumor immunity in preclinical and clinical studies.

Conclusion

Conclusion. TIGIT is a promising immunotherapeutic target in malignant neoplasms of the female reproductive system. Its blockade may improve treatment outcomes in patients with recurrent and resistant cancert ypes. Combined approaches involving anti-TIGIT agents require further clinical validation but even today they offer new directions in targeted therapy and personalized management in gynecologic oncology.

Введение

Введение. Злокачественные новообразования женской репродуктивной системы – рак яичников, эндометрия и шейки матки занимают значительное место в структуре онкологической заболеваемости и смертности у женщин. Стандартные методы лечения, включая хирургическое вмешательство, химио- и лучевую терапию, имеют ограниченную эффективность при рецидивирующих и лекарственно устойчивых формах опухолей. Развитие иммунотерапии, в частности, ингибиторов иммунных контрольных точек (англ. immune checkpoint inhibitors, ICI), открыло новые терапевтические возможности, однако их клиническая эффективность в онкогинекологии остается недостаточной. В связи с этим возрастает интерес к новым мишеням, среди которых выделяется Т-клеточный иммуноглобулин и домен, содержащий ингибирующий мотив на основе тирозина (англ. T-cell immunoglobulin and ITIM domain, TIGIT), коингибирующий рецептор, экспрессируемый на T- и NK-клетках (англ. natural killer cells; естественные киллеры) и играющий важную роль в формировании иммуносупрессивного опухолевого микроокружения.

Цель

Цель: систематизировать современные данные о биологической функции TIGIT и его лигандов, участии в иммуносупрессии при злокачественных опухолях женской репродуктивной системы, а также оценить терапевтический потенциал его блокады в рамках персонализированной иммунотерапии.

Материалы и методы

Материалы и методы. Обзор подготовлен по методологии PRISMA. Проведен систематический поиск публикаций за 2013–2024 гг. в базах PubMed/MEDLINE, Scopus, Web of Science, Embase, Google Scholar и ClinicalTrials.gov. Включены 91 научный источник и 7 зарегистрированных клинических исследований. Оценивались оригинальные статьи, метаанализы, обзоры, руководства и отчеты по клиническим испытаниям.

Результаты

Результаты. TIGIT взаимодействует с рядом лигандов (CD155, CD112, Nectin-4, Fap2), что приводит к подавлению активности NK-клеток и CD8+ Т-клеток, поляризации макрофагов в M2-фенотип, активации регуляторных T-клеток (англ. regulatory T cells, Treg) и нарушению антигенпрезентации. TIGIT коэкспрессируется с белком программируемой клеточной гибели 1 (англ. programmed cell death protein 1, PD-1) и CD96, формируя иммуносупрессивную сигнальную сеть. Повышенная экспрессия TIGIT ассоциирована с прогрессированием рака яичников, эндометрия и шейки матки, сниженной цитотоксичностью опухоль-инфильтрирующих лимфоцитов (англ. tumor-infiltrating lymphocytes, TIL) и неблагоприятным прогнозом. Блокада TIGIT, особенно в комбинации с PD-1/PD-L1 (англ. programmed cell death ligand 1; лиганд программируемой клеточной гибели 1), восстанавливает активность эффекторных клеток и усиливает иммунный ответ в доклинических и клинических исследованиях.

Заключение

Заключение. TIGIT является перспективной иммунотерапевтической мишенью при злокачественных опухолях женской репродуктивной системы. Его блокада может повысить эффективность лечения у пациенток с рецидивирующими и резистентными опухолями. Комбинированные схемы с использованием анти-TIGIT препаратов требуют дальнейшей клинической валидации, но уже сегодня открывают новые направления в таргетной терапии и персонализированном подходе в онкогинекологии.

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