Comprehensive Assessment of the Immunophenotype of Peripheral Blood Lymphocytes, Inflammatory Factors, the Immunophenotype of Lymphocytes Infiltrating the Tumor, and Clinical Indicators for Overall Survival and Progression-Free Survival in Patients with Gastric Cancer

Abstract

To study the state of cellular immunity and local immunity in patients with gastric adenocarcinoma.From 2017 to 2018 at the N.N. Blokhin NMRC of Oncology 45 primary patients with gastric adenocarcinoma (25 - with stages I – III, 20 - with stage IV) received surgical/combined treatment or chemotherapy, 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, degree of differentiation (G), Lauren type and MSI status 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%CI0.782–0.957,p=0.005), and poor prognosis - an increase in NK cells; HR1.382,95%CI1.087–1.758,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%CI1.06-1.89,p=0.017 and HR1.64,95%CI1.12–2.40,p=0.011).At the same time, an increase in the age of patients, the level of neutrophils and platelets (HR1.106, 95%CI1.002-1.199, p=0.015; HR1.714, 95%CI1.063-2.764,p=0.027 and HR1.017,95%CI1.006-1.029, p=0.003) reduce PFS in patients with metastatic gastric cancer. 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.