Abstract
Objective.To study the state of cellular immunity and local immunity in patients with gastric adenocarcinoma.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.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.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.
Highlights
Peripheral blood and tumor tissue were collected before starting treatment
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)
Summary
Г. Комплексная оценка системного и локального иммунитета, факторов воспаления и клинических показателей у больных раком желудка. ФГБУ «Национальный медицинский исследовательский центр онкологии им. Герцена — филиал ФГБУ «Национальный медицинский исследовательский центр радиологии» Минздрава России, Москва, Россия. Изучить состояние системного иммунитета и локального иммунитета у больных аденокарциномой желудка. 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). Показатели локального иммунитета, клеточного состава периферической крови, характеризующие систем‐ ную воспалительную реакцию, и показатели системного иммунитета служат дополнительными прогностическими факторами при раке желудка. Целью данной работы явилось комплексное изучение структуры опухоль-инфильтрирующих лимфоцитов (tumorinfiltrating lymphocytes — TILs), системного иммунитета и индексов воспаления у пациентов с аденокарциномой желудка, а также оценка их прогностической значимости
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