oncotomskСибирский онкологический журналSiberian journal of oncology1814-48612312-3168Tomsk National Research Medical Сепtеr of the Russian Academy of Sciences10.21294/1814-4861-2022-21-2-109-117oncotomsk-2096Research ArticleОБЗОРЫREVIEWSАнализ возможных маркеров эффективного противоопухолевого клеточного иммунного ответа при назначении ингибиторов контрольных точекAnalysis of possible markers of effective antitumor cellular immune response before starting therapy with immune check-point inhibitorshttps://orcid.org/0000-0002-6008-1354МалковаА. М.MalkovaA. M.

 аспирант кафедры онкологии, медицинский факультет

SPIN-код: 3479-1355. Researcher ID (WOS): AAY-3212-2020. Author ID (Scopus): 57213621564

 Россия, 199034, г. Санкт-Петербург, Университетская наб., 7–9 

MD, Postgraduate Student, Department of Oncology

Researcher ID (WOS): AAY-3212-2020. Author ID (Scopus): 57213621564 

7–9, Universitetskaya Emb., 199034, Saint Petersburg, Russia

anya.malkova.95@mail.ruОрловаР. В.OrlovaR. V.

 доктор медицинских наук, профессор, заведующая кафедрой онкологии, медицинский факультет; главный специалист по клинической онкологии и реабилитации

SPIN-код: 9932-6170. Author ID (Scopus): 22836067900 

 Россия, 199034, г. Санкт-Петербург, Университетская наб., 7–9 

 Россия, 198255, г. Санкт-Петербург, пр-т Ветеранов, 56 

MD, Professor, Head of Department of Oncology; Chief Specialist in Clinical Oncology and Rehabilitation

Author ID (Scopus): 22836067900 

7–9, Universitetskaya Emb., 199034, Saint Petersburg, Russia

56, Veteranov Ave., 56, 198255, Saint Petersburg, Russia

ЖуковаН. В.ZhukovaN. V.

 кандидат медицинских наук, доцент кафедры онкологии, медицинский факультет

SPIN-код: 3480-2098 

 Россия, 199034, г. Санкт-Петербург, Университетская наб., 7–9 

 Россия, 198255, г. Санкт-Петербург, пр-т Ветеранов, 56 

 MD, PhD, Associate Professor of the Department of Oncology; Head of theDepartment 

7–9, Universitetskaya Emb., 199034, Saint Petersburg, Russia

56, Veteranov Ave., 56, 198255, Saint Petersburg, Russia

https://orcid.org/0000-0003-3790-7311ГубальА. Р.GubalA. R.

 кандидат химических наук, младший научный сотрудник кафедры аналитической химии, Институт химии

 Россия, 199034, г. Санкт-Петербург, Университетская наб., 7–9 

 PhD, Junior Researcher, Department of Analytical Chemistry, Institute of Chemistry 

7–9, Universitetskaya Emb., 199034, Saint Petersburg, Russia

https://orcid.org/0000-0002-3717-0471ШаройкоВ. В.SharoikoV. V.

 доктор биологических наук, профессор, ведущий научный сотрудник лаборатории биомедицинской химии, Институт химии; ведущий научный сотрудник лаборатории биомедицинского материаловедения  

 Россия, 199034, г. Санкт-Петербург, Университетская наб., 7–9 

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

 DSc, Professor, Leading Researcher, Laboratory of Biomedical Chemistry, Institute of Chemistry; Leading Researcher, Laboratory of Biomedical Materials Science

7–9, Universitetskaya Emb., 199034, Saint Petersburg, Russia

6-8, Tolstoy St., 197022, Saint Petersburg, Russia

ФГБОУ ВПО «Санкт-Петербургский государственный университет»РоссияSaint Petersburg State UniversityRussian FederationФГБОУ ВПО «Санкт-Петербургский государственный университет»; СПб ГБУЗ «Городской клинический онкологический диспансер»РоссияSaint Petersburg State University; Saint Petersburg Clinical Oncology CenterRussian FederationФГБОУ ВПО «Санкт-Петербургский государственный университет»; ФГБОУ ВО «Первый Санкт-Петербургский государственный медицинский университет им. акад. И.П. Павлова»РоссияSaint Petersburg State University; Pavlov First Saint Petersburg State Medical UniversityRussian Federation202208052022212109117Copyright © Малкова А.М., Орлова Р.В., Жукова Н.В., Губаль А.Р., Шаройко В.В., 20222022Малкова А.М., Орлова Р.В., Жукова Н.В., Губаль А.Р., Шаройко В.В.Malkova A.M., Orlova R.V., Zhukova N.V., Gubal A.R., Sharoiko V.V.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/2096

Цель исследования – анализ возможных маркеров эффективного противоопухолевого клеточного иммунного ответа.

Материал и методы

Материал и методы. С помощью ключевых слов: ингибиторы контрольных точек, иммунотерапия, Т-лимфоциты, истощенные Т-лимфоциты, противоопухолевый иммунный ответ – были отобраны обзорные и оригинальные статьи (n=34), опубликованные с 2005 по 2020 г. в международных базах данных Pubmed, Web Of Science, Elsevier.

Результаты

Результаты. Исследование выявило потенциальные маркеры, отражающие высокую активность адаптивного иммунного ответа, основанного на эффективном распознавании антигенов опухоли через молекулы главного комплекса гистосовместимости (MHC), достаточном количестве Т-лимфоцитов и преобладании Т-цитотоксических клеток, а также на низком уровне экспрессии ингибиторных рецепторов и малых молекул. Свою предиктивную значимость показали наличие полиморфизмов единичных нуклеотидов в генах HLA-I и HLA-II, кодирующих белки MHC-I и MHC-II соответственно, высокий уровень лимфоцитов, среди которых наиболее важно преобладание CD8+ Т-клеток и низкий уровень Т-регуляторных клеток (Т-рег), а также наличие полиморфизмов единичных нуклеотидов в генах, кодирующих FcγR рецепторы Т-лимфоцитов. Также была выявлена диагностическая значимость определения экспрессии ингибиторных рецепторов Т-лимфоцитов – TIM3, LAG3, TIGIT, особенно в комплексе с определением уровня экспрессии PD1.

Заключение

Заключение. Полученные результаты могут быть актуальны для внедрения новых методов оценки функциональной активности Т-клеточного иммунного ответа перед назначением ИКТ, а также для разработки новых диагностических панелей, что может представлять интерес для сотрудников клинико-диагностических лабораторий и исследовательских центров.

The aim of the study

The aim of the study. to analyse possible markers of an effective antitumor cellular immune response.

Material and methods

Material and methods. using the keywords «checkpoint inhibitors, immunotherapy, t-lymphocytes, exhausted t-lymphocytes, anti-tumor immune response», review and original articles (n=34) published from 2005 to 2020 in the Pubmed, Web Of Science, Elsevier databases were selected.

Results

Results. the study revealed possible markers reflecting a high activity of an adaptive immune response based on effective recognition of tumor antigens through MHC molecules, a sufficient number of T-lymphocytes and a predominance of T-cytotoxic cells, as well as a low level of expression of inhibitory receptors and small molecules. the presence of single nucleotide polymorphisms in the HLA-I and HLA-II genes encoding MHC-I and MHC-II proteins, respectively, a high level of lymphocytes, among which the most important is the predominance of CD8+ t cells and a low level of T-regulatory cells (T-reg), as well as the presence of single nucleotide polymorphisms in the genes encoding FcγR receptors of T-lymphocytes showed their predictive significance. the diagnostic significance of determining the expression of inhibitory receptors for T-lymphocytes (TIM3, LAG3, TIGIT), especially in combination with the determination of PD-1 expression, was also revealed.

Conclusion

Conclusion. the results obtained may be relevant for applying new methods for the assessment of the functional activity of the T-cell immune response before starting therapy with checkpoint inhibitors, as well as for the development of new diagnostic panels, which may be of interest to employees of clinical diagnostic laboratories and research centers.

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