Advances in Molecular OncologyAdvances in Molecular OncologyУспехи молекулярной онкологии2313-805X2413-3787Publishing House ABV Press37810.17650/2313-805X-2021-8-3-34-43REVIEW ARTICLESОБЗОРНЫЕ СТАТЬИCirculating predictive markers of immune checkpoint inhibitors in non-small cell lung cancerЦиркулирующие предиктивные маркеры ответа на ингибиторы контрольных точек иммунитета при немелкоклеточном раке легкогоhttps://orcid.org/0000-0002-7570-2256MusaelyanA. A.МусаелянА. А.
Russian Federation

6–8 L’va Tolstogo St., Saint Petersburg 197022

177 Mira St., Veseloe village, Sochi, Adler District, Krasnodar Territory 354376

197022 Санкт-Петербург, ул. Льва Толстого, 6–8

354376 Краснодарский край, Сочи, Адлерский р-н, с. Веселое, ул. Мира, 177

https://orcid.org/0000-0001-8698-7018AkopovA. L.АкоповА. Л.
Russian Federation

177 Mira St., Veseloe village, Sochi, Adler District, Krasnodar Territory 354376

354376 Краснодарский край, Сочи, Адлерский р-н, с. Веселое, ул. Мира, 177

https://orcid.org/0000-0002-4998-3699LapinS. V.ЛапинС. В.
Russian Federation

177 Mira St., Veseloe village, Sochi, Adler District, Krasnodar Territory 354376

354376 Краснодарский край, Сочи, Адлерский р-н, с. Веселое, ул. Мира, 177

https://orcid.org/0000-0002-9354-8790NazarovV. D.НазаровВ. Д.
Russian Federation

177 Mira St., Veseloe village, Sochi, Adler District, Krasnodar Territory 354376

354376 Краснодарский край, Сочи, Адлерский р-н, с. Веселое, ул. Мира, 177

FillipovD. I.ФилипповД. И.
Russian Federation

177 Mira St., Veseloe village, Sochi, Adler District, Krasnodar Territory 354376

354376 Краснодарский край, Сочи, Адлерский р-н, с. Веселое, ул. Мира, 177

EmanuelV. L.ЭмануэльВ. Л.
Russian Federation

177 Mira St., Veseloe village, Sochi, Adler District, Krasnodar Territory 354376

354376 Краснодарский край, Сочи, Адлерский р-н, с. Веселое, ул. Мира, 177

https://orcid.org/0000-0001-6080-8042OrlovS. V.ОрловС. В.
Russian Federation

6–8 L’va Tolstogo St., Saint Petersburg 197022

177 Mira St., Veseloe village, Sochi, Adler District, Krasnodar Territory 354376

197022 Санкт-Петербург, ул. Льва Толстого, 6–8

354376 Краснодарский край, Сочи, Адлерский р-н, с. Веселое, ул. Мира, 177

I.P. Pavlov First Saint-Petersburg State Medical UniversityФГБОУ ВО «Первый Санкт-Петербургский государственный медицинский университет им. акад. И.П. Павлова» Минздрава РоссииResearch Institute of Medical PrimatologyФГБНУ «Научно-исследовательский институт медицинской приматологии»150920218334430511202105112021Copyright ©; 2021, Musaelyan A.A., Akopov A.L., Lapin S.V., Nazarov V.D., Fillipov D.I., Emanuel V.L., Orlov S.V.Copyright ©; 2021, Мусаелян А.А., Акопов А.Л., Лапин С.В., Назаров В.Д., Филиппов Д.И., Эмануэль В.Л., Орлов С.В.2021Musaelyan A.A., Akopov A.L., Lapin S.V., Nazarov V.D., Fillipov D.I., Emanuel V.L., Orlov S.V.Мусаелян А.А., Акопов А.Л., Лапин С.В., Назаров В.Д., Филиппов Д.И., Эмануэль В.Л., Орлов С.В.https://creativecommons.org/licenses/by/4.0https://umo.abvpress.ru/jour/article/view/378

Immune checkpoint inhibitors (ICIs) alone or in combination with chemotherapy have become one of the key approaches in the treatment of patients with advanced non-small cell lung cancer (NSCLC). Evaluation of level of PD-L1 (ligand of the programmed cell death receptor 1) expression on tumor cells using immunohistochemistry is the only approved option for determining the indications of ICIs in this group of patients. However, despite high level of PD-L1 expression, up to 80 % of patients do not respond to therapy due to the presence of primary or acquired resistance, which determines the limited effectiveness of ICI. In addition, 8–17 % of PD-L1-negative patients with NSCLC are also able to respond to ICIs. The limitation of this marker is that it does not allow assessing both intratumoral and systemic immune status. It is necessary to search for additional predictive markers to improve the accuracy of the selection of candidates for immunotherapy, which will avoid costs, wasted time, and a high risk of immune-related adverse events in potentially unresponsive patients. The attention of researchers is devoted to circulating markers in peripheral blood, as a non-invasive alternative to biopsy for predicting and monitoring the response. This review focuses on the most promising immunological markers in peripheral blood as potential predictors of response to ICIs in patients with advanced NSCLC.

Иммунотерапия ингибиторами контрольных точек иммунитета (ИКТИ) в виде монотерапии или в комбинации с химиотерапией стала одним из ключевых подходов в лечении пациентов с распространенным немелкоклеточным раком легкого (НМРЛ ). Оценка уровня экспрессии PD-L1 (лиганда рецептора запрограммированной клеточной гибели 1) на опухолевых клетках с помощью иммуногистохимического исследования является единственным одобренным методом определения показаний к назначению ИКТИ у этой группы больных. Однако, несмотря на высокий уровень экспрессии данного маркера, до 80 % пациентов не отвечают на терапию в связи с наличием первичной или приобретенной резистентности. Это обусловливает ограниченную эффективность ИКТИ. К тому же у 8–17 % больных НМРЛ с негативной экспрессией PD-L1 наблюдается ответ на данную терапию. Ограничением этого маркера является то, что он не позволяет оценить как внутриопухолевый, так и системный иммунный статус. Необходим поиск дополнительных предиктивных маркеров для повышения точности отбора кандидатов на иммунотерапию, что позволит избежать затрат, потери времени, высокого риска возникновения иммуноопосредованных нежелательных явлений у потенциально не отвечающих на лечение пациентов. Внимание многих исследователей посвящено циркулирующим маркерам в периферической крови как неинвазивной альтернативе биопсии с целью прогнозирования и мониторинга ответа на терапию. Данный обзор посвящен наиболее перспективным иммунологическим маркерам в периферической крови как потенциальным предикторам ответа на ИКТИ у пациентов с распространенным НМРЛ . 

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