Контрольные точки иммунитета в контексте наружного генитального эндометриоза

Наружный генитальный эндометриоз – хроническое рецидивирующее заболевание, патогенез которого остается до конца не изученным. Эндометриоз делит общие черты с опухолевым процессом. Так, для данного заболевания характерно распространение ткани, подобной эндометрию, вне полости матки. Пролиферация и инвазия клеток в эктопических очагах возможна только при нарушении местных процессов иммунной защиты. Одним из механизмов избегания иммунологического надзора, доказанным для опухолевого процесса, является использование контрольных точек иммунитета. Контрольные точки иммунитета представляют собой белки, расположенные на поверхности клеток иммунной системы (преимущественно Т-лимфоцитов). Связывание контрольных точек иммунитета с их лигандами на поверхности опухолевой клетки приводит к ингибированию клеток иммунитета и помогает таким образом опухоли «выжить». В данном обзоре собраны данные литературы об известных на сегодняшний день контрольных точках иммунитета: CTLA-4, PD-1, LAG-3, Tim-3, TIGIT, 4-1BB, GITR. Рассмотрены наиболее изученные их лиганды, такие как: CD80/CD86, PD-1L, Gal-3, Gal-9. В обзоре систематизированы данные о клетках, на которых экспрессируются контрольные точки иммунитета и их белки с ними связывающиеся, приведены примеры опухолей, которые используют данное взаимодействие для защиты от распознавания. Помимо этого, в обзоре описаны препараты – ингибиторы контрольных точек иммунитета, успешно используемые в терапии определенных опухолей. Наряду с отсутствием полноты знаний о патогенезе эндометриоза, на сегодняшний день единственным достоверным методом его диагностики является проведение лапароскопии с визуализацией очагов и последующим их гистологическим исследованием. В обзоре собраны результаты исследований, посвященных изучению некоторых биомаркеров для неинвазивной диагностики эндометриоза: CA-125, MCP-1, IL-6, BDNF и других. Авторами рассмотрены результаты нескольких работ, в которых контрольные точки иммунитета изучались в аспекте наружного генитального эндометриоза. Следует подчеркнуть, что по результатам этих исследований экспрессия контрольных точек иммунитета Т-лимфоцитами и концентрация растворимых форм была значимо повышена среди женщин с эндометриозом. Также в обзоре представлены результаты эксперимента, в котором определение уровня одного из лигандов контрольных точек иммунитета в крови пациенток показало высокую чувствительность и специфичность. Таким образом, изучение контрольных точек иммунитета в качестве механизма, потенциально используемого эндометриоидными клетками для уклонения от иммунологического ответа, а также биомаркеров неинвазивной диагностики является многообещающим направлением. 

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