Expression Of Myeloid Derived Suppressor Cells(MDSCs)in Gastric Cancer And Its Clinical Significance

Objective: To study the phenotypic characteristics, expression pattern of themyeloid derived suppressor cells (MDSCs) in peripheral blood and tumor tissue ofpatients with gastric cancer, and its intrinsical link with clinicopathological factors(tumor differentiation, invasion, metastasis, tumor size), chemotherapy and prognosis ofpatients, wish to provide a new indicator for gastric cancer progression and prognosis,and supply new theoretical foundation and experimental basis for gastric cancerimmunotherapy.Method: Clinical pathological data and peripheral blood was extractted from62gastric cancer patients. Collect peripheral blood of14patients undergoing preoperativeand postoperative (before chemotherapy), and cancer tissue and adjacent tissue of12patients, using immunofluorescence and flow cytometry analysis technology withHLA-DR-negative, CD11b and CD33positive as markers, to detect expressioncharacteristics and laws of HLA-DR-CD33~+CD11b~+MDSCs in the peripheral blood andtumor tissue in patients with gastric cancer. Combined with clinical pathological data,analyze correlation of HLA-DR-CD33~+CD11b~+MDSCs expression in the peripheralblood of patients and patient gender, age, TNM stage, clinical stage, tumordifferentiation, depth of invasion, lymph node metastasis, tumor size, and whetherrecurrence/metastasis. Do statistical analysis using healthy volunteers as controls.Analyze MDSCs expression change before and after surgery (before chemotherapy) ofthe same patients,and MDSCs expression law in the tumor tissue, paraneoplastic tissueand peripheral blood of the same patient, wish to the establish a possible indicator of theprogression and prognosis of gastric cancer.Results:(1) HLA-DR-CD33~+CD11b~+MDSCs expression in peripheral blood ofnewly diagnosed gastric cancer patients before surgery (3.50±2.02)%was significantlyhigher than that in healthy volunteers (0.96±0.35)%(P<0.05);(2) HLA-DR-CD33~+CD11b~+MDSCs expression was significantly correlated with lymphnode metastasis, depth of tumor invasion, tumor differentiation, TNM stage (P<0.05),and had no significant correlation with patient’s age, gender and tumor size and otherfactors (P>0.05);(3)HLA-DR-CD33~+CD11b~+MDSCs expression in gastric carcinomawas significantly higher than in the adjacent tissues and peripheral blood (P<0.01) inthe same patient;(4)MDSCs expression in peripheral blood was reduced significantlyafter surgery (P<0.01),but there was no significant difference ofHLA-DR-CD33~+CD11b~+MDSCs (P>0.05) before and after chemotherapy peripheralexpression;(5)The expression of MDSCs with recurrent/metastatic group wasincreased(P<0.05);(6) Compared with healthy volunteers,HLA-DR-CD33~+CD11b~+MDSCs in gastric patients high expressed negativeco-stimulatory molecules TIM-3, which may be one of the mechanisms mediated tumorimmune escape by MDSCs.Conclusions: The expression of HLA-DR-CD33~+CD11b~+MDSCs may play animportant role in the development of cancer, and closely correlates with lymphaticmetastasis, depth of tumor invasion, grade of histological differentiation, and TNMstages; Periodical check the changes of MDSCs in peripheral blood of cancer may helpto monitoring postoperative recurrence. Also the high expression of TIM-3may be oneof the important mechanisms of tumor immune escape mediated by MDSCs.Ourresearch provides the new theoretics of evaluating progress and prognosis in patientswith cancer, and provides a new target for gastric carcinoma immunotherapy.