tumorsMalignant tumoursMalignant tumours2224-50572587-6813Rosoncoweb10.18027/2224-5057-2020-10-4-5-15tumors-823Research ArticleОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯORIGINAL REPORTSКомплексная оценка системного и локального иммунитета, факторов воспаления и клинических показателей у больных раком желудка. Злокачественные опухолиComprehensive assessment of the systemic and local immunity, inflammatory factors and clinical indicators in patients with gastric cancerХакимоваГ. Г.KhakimovaG.  G.

Гулноз Г. Хакимова, к. м. н., врач‑онколог отделения химиотерапии Ташкентского городского филиала 

Ташкент

Gulnoz G. Khakimova, MD, PhD, oncologist

Tashkent

hgg_doc@mail.ruТрякинА. А.TryakinA.  A.

Алексей А. Трякин, д. м. н., заведующийонкологического отделения лекарственных методов лечения (химиотерапевти‑ческое) № 2

Москва

Alexey A. Tryakin, MD, PhD, DSc, Head of the Oncology Department Drug Methods of Treatment (chemotherapy) 

Moscow

ЗаботинаТ. Н.ZabotinaT.  N.

Татьяна Н. Заботина, д. б. н., заведующийотделением клинико‑лабораторной диагностики

Москва

Tatyana N. Zabotina, MD, DSC Biol, Head of the Department of Clinical and Laboratory Diagnostics

Moscow

ХакимоваШ. Г.KhakimovaSh. G.

Шахноз Г. Хакимова, к. м. н.

Ташкент

 Москва

Shakhnoz G. Khakimova, MD, PhD

Moscow

Ташкентский педиатрический медицинский институт; . РеспубликанскийспециализированныйНаучно-практический Медицинский Центр Онкологии и РадиологииУзбекистанTashkent Pediatric Medical Institute; Republican Specialized Scientific and Practical Medical Center of Oncology and RadiologyUzbekistanФГБУ «Национальный медицинский исследовательский центр онкологии им. Н. Н. Блохина» Минздрава РоссииРоссияN. N. Blokhin National Medical Research Center of OncologyRussian FederationТашкентский педиатрический медицинский институт; МНИОИ им. П. А. Герцена — филиал ФГБУ Национальный медицинский исследовательский центр радиологии» Минздрава РоссииУзбекистанTashkent Pediatric Medical Institute; P. Hertzen Moscow Oncology Research Institute — Branch of the National Medical Research Radiological CentreUzbekistan202007072021104515Copyright © Хакимова Г.Г., Трякин А.А., Заботина Т.Н., Хакимова Ш.Г., 20212021Хакимова Г.Г., Трякин А.А., Заботина Т.Н., Хакимова Ш.Г.Khakimova G.G., Tryakin A.A., Zabotina T.N., Khakimova S.G.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.malignanttumors.org/jour/article/view/823Цель

Цель.Изучить состояние системного иммунитета и локального иммунитета у больных аденокарциномой желудка.

Материалы и методы

Материалы и методы. С 2017 по 2018 г. в ФГБУ НМИЦ онкологии им. Н. Н. Блохина 45 первичных больных с аденокарциномой желудка (25 пациентов имели I–III стадии, 20 — IV стадию) получили хирургическое лечение или химиотерапию, соответственно. Забор биологического материала (периферической крови, опухолевойткани) осуществлялся перед лечением. Методом проточной цитометрии оценивали процентное содержание степени инфильтрации опухолевой ткани лимфоцитами (CD45 + CD14‑TILs), число Т‑клеток (CD3 + CD19‑TILs), В‑клеток (CD3‑CD19 + TILs), NK‑клеток (CD3‑CD16 + CD56 + TILs), CD16 и CD8 эффекторных клеток и их цитотоксического потенциала (ЦТП) (CD16 + Perforin + TILs; CD16ЦТПTILs),  (CD8 + Perforin + TILs;  CD8ЦТПTILs),  регуляторных  Т‑клеток —  NKT‑клеток  (CD3 + CD16 + CD56 + TILs), CD4 (CD4 + CD25 + CD127‑TILs) и CD8 (CD8 + CD11b‑CD28‑TILs) регуляторных клеток и данные параметры системного иммунитета. Методом иммуногистохимии исследовались интратуморальные и стромальные CD4 + TILs, CD8 + TILs субпопуляции лимфоцитов, их соотношение (CD4 + / CD8 + TILs). Проведена оценка прогностической значимости иммунных клеток, факторов воспаления (нейтрофильно‑лимфоцитарного индекса, тромбоцитарно‑лимфоцитарного индекса) и клинических характеристик (возраст пациента, стадия заболевания, степень дифференцировки, тип по Lauren и статус MSI для общей выживаемости (ОВ) и выживаемости без прогрессирования (ВБП).

Результаты

Результаты.Фактором благоприятного прогноза в отношении ВБП у пациентов с локализованными и местно‑распространенными формами рака желудка явилось повышение числа CD3 + CD19‑TILs (ОР 0,865,95 %ДИ 0,782–0,957, р = 0,005), а неблагоприятного прогноза — повышение NK‑клеток (ОР 1,382, 95 %ДИ 1,087–1,758, р = 0,008). Отмечено негативное влияние увеличения содержания NK‑клеток, уровня нейтрофилов в периферической крови на ОВ пациентов с метастатическим раком желудка (мРЖ) (ОР 1,42, 95 % ДИ 1,06–1,89, р = 0,017), (ОР 1,64, 95 % ДИ 1,12–2,40, р = 0,011). Увеличение возраста больных, уровня нейтрофилов и тромбоцитов (ОР 1,106, 95 %ДИ 1,002–1,199, р = 0,015; ОР 1,714, 95 % ДИ 1,063–2,764, р = 0,027 и ОР 1,017, 95 % ДИ 1,006–1,029, р = 0,003) снижают показатель ВБП у пациентов с мРЖ.

Вывод

Вывод. Показатели локального иммунитета, клеточного состава периферической крови, характеризующие системную воспалительную реакцию, и показатели системного иммунитета служат дополнительными прогностическими факторами при раке желудка.

Objective

Objective.To study the state of cellular immunity and local immunity in patients with gastric adenocarcinoma.

Materials and methods

Materials and methods.From 2017 to 2018 45 primary patients with gastric adenocarcinoma (25 — with stages I–III, 20 — with stage IV) received surgical / combined treatment or chemotherapy at the Blokhin Scientific Research Center of Oncology, respectively. Peripheral blood and tumor tissue were collected before starting treatment. The percentage of the degree of infiltration of tumor tissue by lymphocytes (CD45 + CD14‑TILs) was assessed by flow cytometry: T‑cells (CD3 + CD19‑TILs), B‑cells (CD3‑CD19 + TILs), NK‑cells (CD3‑CD16 + CD56 + TILs), effector cells CD16 and CD8 and their cytotoxic potential (CD16 + Perforin + TILs, CD16CTPTILs), (CD8 + Perforin + TILs; CD8CTPTILs); subpopulations of regulatory T‑cells — NKT‑cells (CD3 + CD16 + CD56 + TILs), regulatory CD4‑cells (CD4 + CD25 + CD127‑TILs) and CD8 (CD8 + CD11b‑CD28‑TILs) and parameters of systemic immunity.

Intratumoral and stromal subpopulations of CD4 + TILs, CD8 + TILs, CD4 + / CD8 + TILs ratios were studied by immunohistochemistry. Also, the cellular composition of peripheral blood was investigated. The prognostic significance of immune cells, inflammation factors (neutrophil‑lymphocyte index, platelet‑lymphocyte index) and clinical characteristics (patient»s age (both by years and by groups: up to 45 years, 46–60 years, over 60 years), disease stage, differentiation (G), Lauren type and MSI status were evaluated for overall survival (OS) and progression‑free survival (PFS).

Results

Results.The factor of a favorable prognosis for PFS in patients with local and locally advanced forms of gastric cancer was an increase in the number of CD3 + CD19‑TILs (HR0.865, 95 %CI 0.782–0.957, p = 0.005), and for poor prognosis — an increase in NK‑cells; HR1.382, 95 %CI 1.087–1.758, p = 0.008. There was a negative effect of the relative content of NK‑cells, an increase in the level of neutrophils in the peripheral blood on the OS of patients with metastatic GC (HR1.42, 95 %CI 1.06–1.89, p = 0.017 and HR1.64, 95 %CI 1.12–2.40, p = 0.011). At the same time, an increase in the age of patients, the level of neutrophils and platelets (HR1.106, 95 %CI 1.002–1.199, p = 0.015; HR1.714, 95 %CI 1.063–2.764, p = 0.027 and HR1.017, 95 %CI 1.006–1.029, p = 0.003) reduce PFS in patients with metastatic gastric cancer.

Conclusion

Conclusion.Indicators of local immunity, the cellular composition of peripheral blood, characterizing the systemic inflammatory response, as well as indicators of systemic immunity can serve as additional prognostic factors in gastric cancer.

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