Микроокружение опухоли: формирование иммунного профиля

Микроокружение опухоли (Tumor Microenvironment — ТМЕ) формируется в результате взаимодействия и образования перекрестных связей между опухолевой клеткой и разными типами окружающих клеток. Исследования последних лет показали, что опухоль так перепрограммирует микроокружение, что ТМЕ способствует развитию первичных опухолей, их метастазированию и становится важным регулятором онкогенеза. Под влиянием опухоли значительным изменениям, «редактированию», подвергается иммунный профиль в ТМЕ. Образуется иммунодепрессивная сеть, которая подавляет активность главного эффектора клеточного иммунитета — Т-лимфоцитов. Т-клетки в ТМЕ находятся в состоянии анергии и истощения и характеризуются повышенной экспрессией ингибирующих рецепторов, снижением секреции цитокинов и цитолитической активности. Блокирование ингибиторных рецепторов специфическими антителами может привести к восстановлению функций истощенных Т-клеток. Поэтому восстановление функциональной активности Т-лимфоцитов представляет одну из важных стратегий в иммунотерапии рака. На формирование иммунного профиля влияют накапливающиеся в опухоли генетические аберрации, которые играют важную роль в создании специфического, характерного только для данной опухоли иммунного окружения в ТМЕ. Генетические изменения опухолевых клеток приводят к фенотипическим и функциональным перестройкам лимфоцитов, что позволяет опухоли избегать реакции иммунных клеток. Поскольку многие опухоли возникают после длительного воспаления или проявляют характеристики хронического воспаления по мере прогрессирования, воспаление считается важным фактором формирования ТМЕ, оказывающим влияние на иммунный профиль. Иммунные инфильтраты из разных опухолей человека, ассоциированных с воспалением, могут содержать ценную прогностическую и патофизиологическую информацию. Так, макрофаги в ТМЕ уже стали рассматриваться как информативный маркер и как терапевтическая мишень. Одним из основных механизмов, с помощью которого опухолевые клетки перепрограммируют окружающие клетки, является выделение экзосом — мелких везикул, которые переносят и доставляют белки и нуклеиновые кислоты к другим клеткам. При поглощении экзосом-ного груза в реципиентной клетке происходят молекулярные, транскрипционные и трансляционные изменения, которые оказывают влияние на функции неопухолевых клеток в ТМЕ. Поэтому опухолевые экзосомы представляют собой эффективное средство, с помощью которого опухоль может изменять реактивность иммунных клеток в ТМЕ. Таким образом, наряду с индивидуальным молекулярным и геномным тестированием опухоли, следует обратить внимание на более глубокий анализ иммунного профиля ТМЕ, который представляет собой большой ресурс биомаркеров и мишеней для иммунотерапии.

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