oncotomskСибирский онкологический журналSiberian journal of oncology1814-48612312-3168Tomsk National Research Medical Сепtеr of the Russian Academy of Sciences10.21294/1814-4861-2020-19-4-123-131oncotomsk-1538Research ArticleОБЗОРЫREVIEWSПРЕДИКТИВНЫЕ МАРКЕРЫ ОТВЕТА НА БЛОКАТОРЫ КОНТРОЛЬНЫХ ТОЧЕК ИММУННОГО ОТВЕТАPREDICTIVE RESPONSE MARKERS FOR IMMUNE RESPONSE BLOCKShttps://orcid.org/0000-0002-9844-4536ЯнусГ. А.JanusG. A.

Янус Григорий Аркадьевич, кандидат медицинских наук, младший научный сотрудник SPIN-код: 7502- 5907. Researcher ID (WOS): E-4260-2018. Author ID (Scopus): 36011349100. 

194100, г. Санкт-Петербург, ул. Литовская, 2;197758, г. Санкт-Петербург, п. Песочный, ул. Ленинградская, 68

Grigory A. Yanus, MD, PhD Researcher ID (WOS): E-4260-2018. Author ID (Scopus): 36011349100

2, Litovskaya Street, 194100, St. Petersburg;68, Leningradskaya Street, Pesochny, St. Petersburg

evgeny@imyanitov.spb.ruhttps://orcid.org/0000-0001-5454-5186ИевлеваА. Г.IevlevaA. G.

Иевлева Аглая Геннадьевна, кандидат медицинских наук, научный сотрудник Researcher ID (WOS): P-8305-2016. Author ID (Scopus): 6506417697.

194100, г. Санкт-Петербург, ул. Литовская, 2;197758, г. Санкт-Петербург, п. Песочный, ул. Ленинградская, 68

Aglaya G. Ievleva, MD, PhD, Researcher Researcher ID (WOS): P-8305-2016. Author ID (Scopus): 6506417697

2, Litovskaya Street, 194100, St. Petersburg;68, Leningradskaya Street, Pesochny, St. Petersburg

https://orcid.org/0000-0001-9764-2090СуспицынЕ. Н.SuspitsynE. N.

Суспицын Евгений Николаевич, кандидат медицинских наук, старший научный сотрудник  SPIN-код: 2362-6304. Researcher ID (WOS): P-9775-2016. Author ID (Scopus): 6603370186. 

194100, г. Санкт-Петербург, ул. Литовская, 2;197758, г. Санкт-Петербург, п. Песочный, ул. Ленинградская, 68

Evgeny N. Suspitsin, MD, PhD, Senior Researcher Researcher ID (WOS): P-9775-2016. Author ID (Scopus): 6603370186.

2, Litovskaya Street, 194100, St. Petersburg;68, Leningradskaya Street, Pesochny, St. Petersburg

https://orcid.org/0000-0002-0157-5952ТюринВ. И.TyurinV. I.

Тюрин Владислав Ильич, врач-лабораторный генетик Researcher ID (WOS): AAH-4623-2020. Author ID (Scopus): 56501760600. 

197758, г. Санкт-Петербург, п. Песочный, ул. Ленинградская, 68

Vladislav I. Tyurin, MD, Physician-Laboratory Geneticist Researcher ID (WOS): AAH-4623-2020. Author ID (Scopus): 56501760600

68, Leningradskaya Street, Pesochny, St. Petersburg

https://orcid.org/0000-0002-2216-4845БизинИ. В.BizinI. V.

Бизин Илья Валерьевич, кандидат технических наук, научный сотрудник SPIN-код: 5471-6185. Researcher ID (WOS): Q-7135-2017. Author ID (Scopus): 56938631000. 

197758, г. Санкт-Петербург, п. Песочный, ул. Ленинградская, 68

Ilya V. Bizin, PhD, Researcher Researcher ID (WOS): Q-7135-2017. Author ID (Scopus): 56938631000

68, Leningradskaya Street, Pesochny, St. Petersburg

ГорустовичО. А.GorustovichO. A.

Горустович Ольга Анатольевна, кандидат медицинских наук SPIN-код: 7423-5368.

197758, г. Санкт-Петербург, п. Песочный, ул. Ленинградская, 68

Olga A. Gorustovich, MD, PhD

68, Leningradskaya Street, Pesochny, St. Petersburg

НиВ. И.NiV. I.

Ни Валерия Игоревна, лаборант-исследователь  Author ID (Scopus): 57208783909.

197758, г. Санкт-Петербург, п. Песочный, ул. Ленинградская, 68

Valeria I. Ni, Laboratory Assistant Author ID (Scopus): 57208783909

68, Leningradskaya Street, Pesochny, St. Petersburg

https://orcid.org/0000-0002-4201-8124ХолматовМ. М.KholmatovM. M.

Холматов Максим Михайлович, лаборант-исследователь Author ID (Scopus): 57203189429. 

197758, г. Санкт-Петербург, п. Песочный, ул. Ленинградская, 68

Maxim M. Kholmatov, Laboratory Assistant Author ID (Scopus): 57203189429.

68, Leningradskaya Street, Pesochny, St. Petersburg

https://orcid.org/0000-0003-4988-1796ЛайдусТ. А.LaidusT. A.

Лайдус Татьяна Александровна, лаборант-исследователь.

197758, г. Санкт-Петербург, п. Песочный, ул. Ленинградская, 68

Tatiana A. Laidus, Laboratory Assistant

68, Leningradskaya Street, Pesochny, St. Petersburg

ЧуйнышенаС. А.ChuynyshenaS. A.

Чуйнышена Светлана Андреевна, лаборант

194100, г. Санкт-Петербург, ул. Литовская, 2;

Svetlana A. Chuinysheva, Laboratory Assistant

2, Litovskaya Street, 194100, St. Petersburg

https://orcid.org/0000-0002-2149-7728АлексахинаС. Н.AleksakhinaS. N.

Алексахина Светлана Николаевна, кандидат медицинских наук, научный сотрудник SPIN-код: 6898-4687. Researcher ID (WOS): B-2136-2013. Author ID (Scopus): 56003023200. 

197758, г. Санкт-Петербург, п. Песочный, ул. Ленинградская, 68

Svetlana N. Aleksakhina, MD, PhD Researcher ID (WOS): B-2136-2013. Author ID (Scopus:) 56003023200.

68, Leningradskaya Street, Pesochny, St. Petersburg

https://orcid.org/0000-0003-4529-7891ИмянитовЕ. Н.ImyanitovE. N.

Имянитов Евгений Наумович, доктор медицинских наук, профессор, член-корреспондент РАН, заведующий научным отделом биологии опухолевого роста SPIN-код: 1909-7323. Author ID (Scopus): 7003644486.

194100, г. Санкт-Петербург, ул. Литовская, 2;197758, г. Санкт-Петербург, п. Песочный, ул. Ленинградская, 68;191015, г. Санкт-Петербург, ул. Кирочная, 41

Evgeny N. Imyanitov, MD, Professor, Corresponding Member of the Russian Academy of Sciences, Head of the Department of Tumor Growth Biology Author ID (Scopus): 7003644486.

2, Litovskaya Street, 194100, St. Petersburg;68, Leningradskaya Street, Pesochny, St. Petersburg

Санкт-Петербургский государственный педиатрический медицинский университет; НМИЦ онкологии им. Н.Н. ПетроваРоссияSt. Petersburg State Pediatric Medical University; N.N. Petrov National Medical Research Center of OncologyRussian FederationНМИЦ онкологии им. Н.Н. ПетроваРоссияN.N. Petrov National Medical Research Center of OncologyRussian FederationСанкт-Петербургский государственный педиатрический медицинский университетРоссияSt. Petersburg State Pediatric Medical UniversityRussian FederationСанкт-Петербургский государственный педиатрический медицинский университет; НМИЦ онкологии им. Н.Н. Петрова; Северо-Западный государственный медицинский университет им. И.И. МечниковаРоссияSt. Petersburg State Pediatric Medical University; N.N. Petrov National Medical Research Center of OncologyRussian Federation202001092020194123131Copyright © Янус Г.А., Иевлева А.Г., Суспицын Е.Н., Тюрин В.И., Бизин И.В., Горустович О.А., Ни В.И., Холматов М.М., Лайдус Т.А., Чуйнышена С.А., Алексахина С.Н., Имянитов Е.Н., 20202020Янус Г.А., Иевлева А.Г., Суспицын Е.Н., Тюрин В.И., Бизин И.В., Горустович О.А., Ни В.И., Холматов М.М., Лайдус Т.А., Чуйнышена С.А., Алексахина С.Н., Имянитов Е.Н.Janus G.A., Ievleva A.G., Suspitsyn E.N., Tyurin V.I., Bizin I.V., Gorustovich O.A., Ni V.I., Kholmatov M.M., Laidus T.A., Chuynyshena S.A., Aleksakhina S.N., Imyanitov E.N.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.siboncoj.ru/jour/article/view/1538

Несмотря на беспрецедентный успех применения ингибиторов контрольных точек иммунного ответа в терапии рака легкого, меланомы, гипермутабельных новообразований различной локализации и проч., существенная доля пациентов, получающих препараты этой группы, не демонстрирует ответа на лечение. Предиктивные маркеры, рутинно используемые при отборе больных для прохождения иммунотерапии, в частности уровень экспрессии PD -L1 и наличие микросателлитной нестабильности, имеют определённые ограничения. За последнее десятилетие было предложено множество иных биомаркеров, призванных предсказать эффект на назначение иммунотерапии: внутриопухолевая мутационная нагрузка, состав лимфоцитарного инфильтрата; аллельная композиция главного комплекса гистосовместимости; соотношения между количеством различных форменных элементов крови и ее биохимическими показателями; особенности микрофлоры ЖКТ и т. д. Эти маркеры могут прямо или косвенно отражать иммуногенность самой опухоли, а также состояние системного и внутриопухолевого иммунитета. Предсказательная сила, достоверность и степень их близости к практическому применению чрезвычайно различны. При подготовке данного обзора был проведен поиск литературы последних лет, касающейся изучения предикторов эффективности ингибиторов контрольных точек иммунного ответа, в журналах, входящих в базы данных Pubmed, Web of Science, Scopus.

Despite the unprecedented success in using immune checkpoint inhibitors in the treatment of lung cancer, melanoma, hypermutable tumors of various localization, etc., a significant proportion of patients receiving these drugs do not respond to treatment. Predictive markers routinely used in the selection of patients for immunotherapy, in particular, the level of expression of PD -L1 and the presence of microsatellite instability, have certain limitations. Over the past decade, many other biomarkers designed to predict response to immunotherapy have been proposed, namely: tymor mutation burden, composition of lymphocytic infiltrate; allelic composition of the major histocompatibility complex; relationship between the numbers of different formed elements of blood as well as between its biochemical parameters; microflora of the digestive tract, etc. These markers can directly or indirectly reflect the immunogenicity of the tumor itself, as well as the state of systemic and intratumoral immune response. The predictive power and reliability of these markers are extremely different. When preparing this review, we conducted a literature search for recent studies regarding predictors of efficacy for immune checkpoint inhibitors published in the journals included in the databases, such as Pubmed, Web of Science, and Scopus.

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The authors declare that there are no conflicts of interest present.