| [Objective]To explore FOXP3+Treg cells,CD 163+M2 macrophages,CD3+T lymphocytes,CD8+T lymphocytes and PD-L1 in different subtypes of gastric cancer by clinicopathological data and indicate their diverse prognostic value;and to analysis the expression of OX40 and PD1 on FOXP3+regulatory T cells infiltrated in gastric cancer tumor microenvironment,which may direct further understanding of the immune heterogeneity of gastric cancer and provide promising immunotherapeutic approaches for the treatment of gastric cancer in the future.[Methods]A total of 598 surgically resected FFPE primary gastric cancer samples(including 68 paired hepatic metastasis lesions)are assessed for the markers of FOXP3,CD 163,CD3,CD8,PD-L1.Subgroups were analyzed according to the clinicopathological data and corresponding prognosis.Subsequently,20 cases of fresh gastric cancer samples were collected to detect the expression of OX40 and PD-1 on FOXP3+regulatory T cells infiltrated in tumor microenvironment as well as their functional markers by FACS.[Results]PD-L1,CD3,CD8 could be regarded as favourable prognostic factors.Our data demonstrated that high infiltration of FOXP3+Treg indicates better prognosis in stage Ⅰ-Ⅱ patients,with the converse outcome in stage Ⅲ-Ⅳ patients.It also show different prognositic value in different pathological classifications,chemotherapy strategies,locations,with or without lymph node metastasis.In addition,M2 macrophages indicated poor prognosis in general,however,it suggest a favorable prognosis when highly infiltrated in signet ring cell carcinoma and mucinous adenocarcinoma.Besides,the infiltration of FOXP3+Tregs is found significantly higher in primary tumor lesions than paired hepatic metastatic lesions.In addition,in the gastric cancer microenvironment,the functional biomarkers CTLA-4,CD25 and FOXP3 in OX40+FOXP3+Treg cells were upregulated when compared with the OX40-Treg subset,while there was no significant difference between the PD-1+FOXP3+Treg and PD-1FOXP3+Treg subsets.There is a significant difference about the expression of OX40 and PD-1 in different immune cells infiltrated in the gastric cancer tumor microenvironment,and the PD-L1/PD-1 signal axis may weaken the tumor infiltrating Tregs of gastric cancer.[Conclusions]These results suggest that different subgroups of gastric cancer can show different immune status,while different subsets of Treg cells in gastric cancer tumor microenvironment may exhibit different functions.Through this study,we can further deepen the understanding of the immune status of different subtypes of gastric cancer,and provide further theoretical basis and potential targets for the future immunotherapy of gastric cancer. |
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