Иммуносупрессивная роль TIGIT в опухолях женской репродуктивной системы: от механизма к терапии

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: 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. 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. 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. 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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