Advances in Molecular OncologyAdvances in Molecular OncologyУспехи молекулярной онкологии2313-805X2413-3787Publishing House ABV Press53810.17650/2313-805X-2023-10-2-17-29REVIEWОБЗОРНАЯ СТАТЬЯImmunotherapy of gastrointestinal stromal tumors: current view and future directionsИммунотерапия гастроинтестинальных стромальных опухолей: состояние вопроса и перспективыhttps://orcid.org/0000-0003-2415-1084BoichukS. V.БойчукС. В.
Russian Federation

Sergei V. Boichuk - Department of Pathology of Kazan State Medical University, Ministry of Health of Russia; “Biomarker” Research Laboratory, Institute of Fundamental Medicine and Biology, Kazan Federal University, Department of Radiotherapy and Radiology of Russian Medical Academy of Continuing Professional Education, Ministry of Health of Russia.

49 Butlerova St., Kazan 420012; Bld. 1, 18 Kremlevskaya St.; Kazan 420008; Bld. 1, 2/1 Barricadnaya St., Moscow 125993

Бойчук Сергей Васильевич - кафедра общей патологии ФГБОУ ВО «КГМУ» Минздрава России; Научно-исследовательская лаборатория «Биомаркер», Институт фундаментальной медицины и биологии, ФГАОУ ВО «КФУ»; кафедра радиотерапии и радиологии ФГБОУ ДПО «РМАНПО» Минздрава России.

420012 Казань, ул. Бутлерова, 49; 420008 Казань, ул. Кремлевская, 18, корп. 1; 125993 Москва, ул. Баррикадная, 2/1, стр. 1

boichuksergei@mail.ruAbduraevaS. A.АбдураеваС. А.
Russian Federation

Department of Pathology of Kazan State Medical University, Ministry of Health of Russia.

49 Butlerova St., Kazan 420012

Кафедра общей патологии ФГБОУ ВО «КГМУ» Минздрава России.

420012 Казань, ул. Бутлерова, 49

https://orcid.org/0000-0002-2078-4274KopninP. B.КопнинП. Б.
Russian Federation

24 Kashirskoye Shosse, Moscow 115522

115522 Москва, Каширское шоссе, 24

Kazan State Medical University, Ministry of Health of RussiaФГБОУ ВО «Казанский государственный медицинский университет» Минздрава РоссииKazan Federal UniversityФГАОУ ВО «Казанский (Приволжский) федеральный университет»Russian Medical Academy of Continuing Professional Education, Ministry of Health of RussiaФГБОУ ДПО «Российская медицинская академия непрерывного профессионального образования» Минздрава РоссииN.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of RussiaФГБУ «Национальный медицинский исследовательский центр онкологии им. Н.Н. Блохина» Минздрава России1505202310217291905202310072023Copyright ©; 2023, Boichuk S.V., Abduraeva S.A., Kopnin P.B.Copyright ©; 2023, Бойчук С.В., Абдураева С.А., Копнин П.Б.2023Boichuk S.V., Abduraeva S.A., Kopnin P.B.Бойчук С.В., Абдураева С.А., Копнин П.Б.https://creativecommons.org/licenses/by/4.0https://umo.abvpress.ru/jour/article/view/538

Gastrointestinal stromal tumors (GIST) are most common mesenchymal tumors in gastrointestinal tract which originate from interstitial cells of Cajal and characterized by the mutations in the KIT or PDGFRA tyrosine kinase receptors. Thus, the common therapeutic approach for GIST therapy (including metastatic, recurrent and non-resectable forms) is based on inhibiton of activities of receptor tyrosine kinases indicated above by corresponding receptor tyrosine kinase inhibitors, including first-line therapeutic agent imatinib mesylate – Gleevec. Despite of high efficacy of IM-based therapy, most of GIST patients acquire resistance to this receptor tyrosine kinase inhibitor, which in turn requires second-, third- and fourth-line therapies. The review also describes the common molecular and genetic variants of GIST and the mechanisms of primary and secondary GIST resistance to the targeted-based therapies. In addition, the role of immune microenvironment in GIST and its relationship with tumor’s mutational burden are discussed in detail, thereby illustrating the immunotherapy as one of the attractive future directions for GIST therapy. Lastly, the manuscript provides the information about the ongoing clinical trials of GIST immunotherapy.

Гастроинтестинальные стромальные опухоли (ГИСО) происходят от веретеновидных интерстициальных клеток кахаля и характеризуются наличием мутаций в генах KIT и PDGFRA, кодирующих одноименные тирозинкиназные  рецепторы. Основным принципом лекарственной терапии пациентов с данными новообразованиями (в том числе неоперабельных, рецидивирующих и метастатических форм) является назначение им таргетных препаратов, ингибирующих активность вышеуказанных рецепторных тирозинкиназ. Несмотря на высокую эффективность этих лекарственных средств, в первую очередь иматиниба мезилата (гливека), в лечении ГИСО, у подавляющего большинства пациентов спустя 1,5–2 года после начала таргетной терапии развивается резистентность опухоли к данным препаратам, что диктует необходимость пересмотра тактики лечения и последующего назначения препаратов терапии 2, 3 и 4-й линий. в обзоре рассматриваются основные молекулярно-генетические варианты ГИСО, современные принципы их лечения, а также механизмы первичной и вторичной резистентности данных новообразований к таргетным препаратам. Также описываются механизмы взаимодействия клеток иммунной системы с ГИСО, взаимосвязь мутационного и иммунного профилей опухолей, перспективные подходы к иммунотерапии этих новообразований и приводятся данные о текущих клинических испытаниях, направленных на коррекцию основных звеньев иммунной системы у пациентов с ГИСО.

gastrointestinal stromal tumorsmolecular and genetic profileprimary resistancesecondary resistancetargeted drugsimmune microenvironmentimmunotherapyгастроинтестинальные стромальные опухолимолекулярно-генетический профильпервичная резистентностьвторичная резистентностьтаргетные препаратыиммунное микроокружениеиммунотерапияThe study was carried out with the support of the Russian Science Foundation (Grant No. 20-15-00001) and has been supported by the Kazan Federal University of Ministry of Health of Russia Strategic Academic Leadership Program (PRIORITY-2030).Исследование выполнено при поддержке Российского научного фонда (Грант № 20-15-00001) за счет средств Программы стратегического академического лидерства Казанского (Приволжского) федерального университета (ПРИОРИТЕТ-2030).Kindblom L.G., Remotti H.E., Aldenborg F., Meis-Kindblom J.M. Gastrointestinal pacemaker cell tumor (GIPACT): gastrointestinal stromal tumors show phenotypic characteristics of the interstitial cells of Cajal. 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