The Expression Of Foxp3~+ Regulatory T Cells And Its Effects On Gastric Cancer After Radical Resection

PurposeThe aim of the present study was to investigate the expression and the prognostic value of tumor-infiltrated lymphocytes (TILs), especially the prognostic value of Foxp3+ regulatory T cells (Tregs) in gastric cancer patients after radical resection.Patients and MethodsFrom 135 patients, who underwent R0 resections with extended lymph nodes dissection (D2) between 1999 and 2005 at Zhongshan Hospital of Fudan Uniersity, CD4+, CD8+ and Foxp3+ TILs were assessed by immunohistochemistry in tissue microarrays and N1 regional lymph nodes sections containing gastric cancer. Prognostic effects of low or high-density TIL subsets were evaluated by Cox regression and Kaplan-Meier analysis using median values as cutoff.ResultsThe frequency of CD4+, CD8+ or FOXP3+ TILs in tumor sites was significantly higher than that in normal tissues (Wilcoxon Test, p<0.01). It was found that CD4+, CD8+ TILs FOXP3+/CD8+ ratio and FOXP3+/CD4+ ratio were not associated with overall survival (OS). In the tumor sites, high Tregs density was an independent factor for worse OS (Multivariate analysis HR 2.598,p=0.004). One-year, two-year, three-year and four-year OS rates were 82.6%,65.2%,60.4% and 55.6% for the group with intratumoral high Tregs density, compared with 83.3%,81.8%,77.3% and 77.3% for the group with intratumoral low density (Logrank-test p=0.009). Although the infiltration of Foxp3+ Tregs in N1 regional lymph nodes was associated with lymph nodes metastasis (p=0.043), it wasn't associated with prognosis (Logrank-test p=0.257).ConclusionsIntratumoral high Foxp3+ Tregs density was an independent predictor for the prognosis of gastric cancer. It can be inferred that deletion of Tregs may be an effective immunotherapy to prolong survival after surgery.