Russian Journal of BiotherapyRussian Journal of BiotherapyРоссийский биотерапевтический журнал1726-97841726-9792Publishing House ABV Press117410.17650/1726-9784-2019-18-4-06-16REVIEWSОБЗОРЫ ЛИТЕРАТУРЫGASTRIC CANCER IMMUNOTHERAPYИММУНОТЕРАПИЯ РАКА ЖЕЛУДКАhttps://orcid.org/0000-0003-1561-2504MansorunovD. Zh.МансоруновД. Ж.
Russian Federation

1 Moskvorechye St., Moscow 115522, Russia

Россия, 115522 Москва, ул. Москворечье 1

gah3ah@gmail.comhttps://orcid.org/0000-0002-8495-7728AlimovA. A.АлимовА. А.
Russian Federation

1 Moskvorechye St., Moscow 115522, Russia

Россия, 115522 Москва, ул. Москворечье 1

https://orcid.org/0000-0003-4539-5424ApanovichN. V.АпановичН. В.
Russian Federation

1 Moskvorechye St., Moscow 115522, Russia

Россия, 115522 Москва, ул. Москворечье 1

https://orcid.org/0000-0001-6156-9725KuzevanovaA. Yu.КузевановаА. Ю.
Russian Federation

1 Moskvorechye St., Moscow 115522, Russia

Россия, 115522 Москва, ул. Москворечье 1

https://orcid.org/0000-0002-7673-4284BogushT. A.БогушТ. А.
Russian Federation

24 Kashirskoye Shosse, Moscow 115478, Russia

Россия, 115478 Москва, Каширское шоссе, 24

https://orcid.org/0000-0002-5229-8203StilidiI. S.СтилидиИ. С.
Russian Federation

24 Kashirskoye Shosse, Moscow 115478, Russia

Россия, 115478 Москва, Каширское шоссе, 24

https://orcid.org/0000-0002-7001-9116KarpukhinA. V.КарпухинА. В.
Russian Federation

1 Moskvorechye St., Moscow 115522, Russia

Россия, 115522 Москва, ул. Москворечье 1

Bochkov Research Centre for Medical GeneticsФГБНУ «Медико-генетический научный центр им. академика Н. П. Бочкова»N.N. Blokhin National Medical Research Center of Oncology of the Ministry of Health of the Russian FederationФГБУ «Национальный медицинский исследовательский центр онкологии им. Н. Н. Блохина» Минздрава России021220191846163011201930112019https://bioterapevt.abvpress.ru/jour/article/view/1174

Gastric cancer (GC) takes 5th place among the malignant neoplasms by incidence in the world. Mortality from GC is high, since in most cases the disease is diagnosed in the late stages, with distant metastases, the five-year survival in GC does not exceed 25–30 %. The standard for GC therapy is surgery with chemotherapy. There is a high resistance to chemotherapy in the late stages of GC, and this circumstance requires a fundamentally new therapy. Recently, studies have been actively conducted on the therapy of GC with the immune control point inhibitors. At the moment, the most studied are monoclonal antibodies against PD-1 (Programmed cell death 1, CD279) / PDL1 (Programmed death-ligand 1, CD274), CTLA-4 (Cytotoxic T-lymphocyte-associated protein 4, CD152). The article discusses the characteristics of PD-1, PD-L1, CTLA-4 molecules and their significance in suppressing the T-cell response, as well as the antitumor effect of immune control point inhibitors. The results of clinical studies of GC therapy with monoclonal antibodies against PD-1 / PD-L1, CTLA-4 were analyzed. The immune control point inhibitors are used as both first-line therapy and subsequent ones. The negative side of immunotherapy is immune-mediated adverse events that can affect the tissues of the kidneys, heart, gastrointestinal tract, liver, lungs, skin and endocrine glands. Biomarkers of the effectiveness of the immune control point inhibitors for GC are considered, among which one can distinguish PD-L1 expression, microsatellite instability, gene expression profile, tumor mutational load and composition of the intestinal microbiome.

Рак желудка (РЖ) занимает 5-е место среди злокачественных новообразований по заболеваемости в мире. Смертность от РЖ высока, так как в большинстве случаев заболевание диагностируется на поздних стадиях, с отдаленными метастазами, 5-летняя выживаемость больных РЖ не превышает 25–30 %. Стандартом терапии РЖ является хирургическое вмешательство с химиотерапией. На поздних стадиях РЖ наблюдается высокая резистентность к химиотерапии, в связи с чем существует острая необходимость в принципиально новой терапии. В последнее время активно проводятся исследования терапии РЖ ингибиторами контрольных точек иммунитета. На данный момент наиболее изучены моноклональные антитела против PD-1 (Programmed cell death 1, CD279) / PD-L1 (Programmed death-ligand 1, CD274), CTLA-4 (Cytotoxic T-lymphocyte-associated protein 4, CD152). В статье рассмотрены характеристики молекул PD-1, PD-L1, CTLA-4 и их значение в супрессии Т-клеточного ответа, а также противоопухолевый эффект ингибиторов контрольных точек иммунитета. Проанализированы результаты клинических исследований терапии РЖ моноклональными антителами против PD-1 / PDL1, CTLA-4. Ингибиторы контрольных точек иммунитета находят применение как в качестве первой, так и последующих линий терапии. Отрицательной стороной иммунотерапии являются иммуноопосредованные нежелательные явления, которые могут поражать ткани почек, сердца, желудочно-кишечного тракта, печени, легких, кожи, эндокринных желез. Рассмотрены биомаркеры эффективности терапии РЖ ингибиторами контрольных точек иммунитета, среди которых можно выделить экспрессию PD-L1, микросателлитную нестабильность, профиль экспрессии генов, мутационную нагрузку опухоли и состав микробиоты кишечника.

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