Advances in Molecular OncologyAdvances in Molecular OncologyУспехи молекулярной онкологии2313-805X2413-3787Publishing House ABV Press38610.17650/2313-805X-2021-8-4-21-28REVIEW ARTICLESОБЗОРНЫЕ СТАТЬИImmunology and prospects of immunotherapy against malignant gliomas: humoral immunityИммунология и перспективы иммунотерапии злокачественных глиом: использование факторов гуморального иммунитетаhttps://orcid.org/0000-0003-0390-8498KulyovaS. A.КулеваС. А.
Russian Federation

Svetlana Aleksandrovna Kuleva

68 Leningradskaya St., Pesochnyy Settlement, Saint Petersburg 1977582 Litovskaya St., St. Petersburg 194100

Светлана Александровна Кулева

197758 Санкт-Петербург, пос. Песочный, ул. Ленинградская, 68194100 Санкт-Петербург, ул. Литовская, 2

Kulevadoc@yandex.ruhttps://orcid.org/0000-0002-5004-1543BorokshinovaK. M.БорокшиноваК. М.
Russian Federation

68 Leningradskaya St., Pesochnyy Settlement, Saint Petersburg 197758

197758 Санкт-Петербург, пос. Песочный, ул. Ленинградская, 68

https://orcid.org/0000-0003-1308-8622DruyA. E.ДруйА. Е.
Russian Federation

1 Samory Mashela St., GSP-7, Moscow 11799722a Karl Marks St., Yekaterinburg 620026

117997 Москва, ГСП-7, ул. Саморы Машела, 1620026 Екатеринбург, ул. Карла Маркса, 22а

N.N. Petrov National Medical Research Center of Oncology, Ministry of Health of RussiaФГБОУ «Национальный медицинский исследовательский центр онкологии им. Н.Н. Петрова» Минздрава РоссииSaint Petersburg State Pediatric Medical University of the Ministry of Health of RussiaФГБОУ ВО «Санкт-Петербургский государственный педиатрический медицинский университет» Минздрава РоссииDmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology Ministry of Health of RussiaФГБОУ «Национальный медицинский исследовательский центр детской гематологии, онкологии и иммунологии им. Дмитрия Рогачева» Минздрава РоссииCenter for Specialized Types of Medical Care Institute of Medical Cell TechnologiesГАУЗ «Центр специализированных видов медицинской помощи «Институт медицинских клеточных технологий»151220218421281712202117122021Copyright ©; 2021, Kulyova S.A., Borokshinova K.M., Druy A.E.Copyright ©; 2021, Кулева С.А., Борокшинова К.М., Друй А.Е.2021Kulyova S.A., Borokshinova K.M., Druy A.E.Кулева С.А., Борокшинова К.М., Друй А.Е.https://creativecommons.org/licenses/by/4.0https://umo.abvpress.ru/jour/article/view/386

High-grade gliomas are aggressive brain tumors with limited survival rates. To date the maximum of survival benefit of conventional therapeutic options has been already reached and innovative treatment strategies, based on tumor biology are urgently needed. Generally, malignant gliomas, including glioblastoma, are immunologically “cold: neoplasms, with weak anti-tumor immune response and peritumoral inflammation, caused by reduced expression of neoantigens by tumor cells and restricted immunoreactivity of the microenvironment. The reduced immunogenicity of brain structures is conditioned by the absence of homing molecules for white blood cells on them, as well as the suppression of activated (CD178+) T cells by brain gangliosides. The cell population infiltrating malignant glioma is impoverished with cytotoxic T cells (CD8+ FOXP3–) and oppositely enriched with regulatory T cells and type 2 macrophages (M2). An effective anti-glioma immune response is resulted in increasing the total number of tumor-infiltrating lymphocytes and the CD8+ cell content; switching the functional activity of macrophages from M2 to M1 type. Integration of immunotherapeutic technologies (vaccines and monoclonal antibodies) into treatment strategies of malignant gliomas is relevant and promising approach based on biological features of the tumor.

Глиомы высокой степени злокачественности – агрессивные опухоли центральной нервной системы. Стандартная химиолучевая терапия данных новообразований не является куративной опцией, поэтому попытки усиления и индивидуализации их лечения на сегодняшний день предполагают воздействие на патогенетические механизмы роста опухоли на клеточном и молекулярно-генетическом уровнях. Злокачественные глиомы, в первую очередь глиобластомы, являются «холодными» опухолями, в которых иммунный ответ и перитуморальное воспаление проявляются слабо. Это объясняется сниженной экспрессией неоантигенов опухолевыми клетками и низкой иммунореактивностью микроокружения. Клетки центральной нервной системы лишены молекул для хоминга лейкоцитов, а поверхностные соединения – ганглиозиды – оказывают прямое ингибирующее воздействие на CD178+-цитотоксические Т-лимфоциты. Это приводит к тому, что популяция лейкоцитов, инфильтрирующих опухоль, представлена в основном клетками, отрицательно регулирующими иммунный ответ (регуляторными (CD4+ CD25+ FOXP3+) T-лимфоцитами и макрофагами 2-го типа). Макрофаги 2-го типа ингибируют клеточный иммунный ответ, стимулируют неоангиогенез и создают условия для метастатического распространения клеток опухоли.

Интеграция в лечении опухолей центральной нервной системы иммунотерапевтических подходов, в том числе применение вакцин и моноклональных антител, является актуальной стратегией, основанной на биологических свойствах опухолевой ткани.

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