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Внедрение иммунотерапии в практику лечения метастатического колоректального рака совершило революцию в этой области онкологии, как и во многих других: до 30-40 % неизлечимых больных, которым показаны ингибиторы контрольных точек иммунного ответа (ИКТИО), демонстрируют стойкий ответ на лечение. До недавнего времени при колоректальном раке назначение иммунотерапии зависело от бинарного молекулярного/иммуногистохимического предиктора: наличия или отсутствия микросателлитной нестабильности/дефекта репарации неспаренных оснований ДНК в диссеминированной опухоли толстой кишки. В настоящее время возможности применения ИКТИО при раке толстой кишки (РТК) быстро расширяются. Так, доказана их польза в неоадъювантном режиме и при выявлении наследственных и соматических мутаций в генах ДНК-полимераз, обладающих редактирующим действием (POLE/POLD1). Выполнен колоссальный объем исследований, призванных охарактеризовать биологическую роль и клиническую значимость мутационной опухолевой нагрузки, отдельных драйверных мутаций, экспрессионных характеристик опухолевой клетки, микроокружения опухоли, системного состояния иммунитета и т. д. Настоящий обзор призван осветить современные представления о роли и механизмах влияния высокой мутационной опухолевой нагрузки, связанной и не связанной с микросателлитной нестабильностью/дефицитом системы репарации неспаренных оснований ДНК, на реализацию эффекта иммунотерапии.
Библиографические ссылки
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