The Expression Of Tregs And CD8~+T Cells In Malignant Melanoma And The Correlation With Prognosis

Objective:To analyze infiltration of Tregs（Regulatory T cells,Tregs）and CD8⁺T cells in malignant melanoma in the local immune microenvironment,and their relationship with the prognosis,and discusses the infiltration of two indexes in mucosal malignant melanoma and cutaneou malignant melanoma in the local immune microenvironment.To analysis the relationship between number of Treg and CD8⁺T cell and prognosis.Methods:This study was a retrospective study.From January 2003 to June 2014,pathological specimens of 58 patients with malignant melanoma were reviewed.Of which,21 cases were mucosal malignant melanoma,37 cases were cutaneous malignant melanoma.Immunohistochemistry was used to assess the expression of Foxp3⁺Tregs and CD8⁺T cells in tumor microenvironment of 58 patients with malignant melanoma.The correlation between this two factors and clinicopathologic characteristics,as well as the prognosis value,were analyzed.Theχ2 test was used to compare measurement data,count data were compared using t-test,correlation analysis using Spearman rank correlation test.Survival was analyzed by the Kaplan-Meier method.and theχ2 test for balance examination on the clinical data of every two groups.Results:The number of Foxp3⁺Tregs in mucosa malignant melanoma（11.81+5.446）/100lymphocytes is significantly higher than that in cutaneous malignant melanoma（8.47+3.894）/100 lymphocytes,t=2.648,P=0.011;In the group of diameter≥3 cm,Foxp3^highTregs account for 63.0%,higher than that in the group of diameter of<3 cm（35.5%）,P<0.05.In the group of patients with lymph node metastasis,Foxp3^highTregs account for 66.7%,higher than that in the group of no lymph node metastasis（35.3%）,（P<0.05）.Foxp3^highTregs accounted for 72.2%in the group of patients with distant metastasis which was higher than that of group with no distant metastasis（37.5%）,（P<0.05）.In addition,the number of CD8⁺T cells and presence of ulceration have significant correlation.CD8^high group,accounting for 33.3%in the group of patients with ulceration,is significantly higher than that of no ulceration（5.9%）,（P<0.05）.Further,we found that whether there was a significant correlation between CD8⁺T cells/Treg and presence of ulceration and distant metastasis.In the group of presence of ulceration and distant metastasis,the ratio of CD8⁺T cells/Treg was higher than that in the group of no presence of ulceration and no distant metastasis,P<0.05.However,there was no statistically significant difference between the two groups occurred in cutaneous and mucosal.But there might be a tendency that the proportion of CD8⁺T cells/Treg in malignant melanoma occurred in mucosal was lower than that in malignant melanoma occurred in cutaneous.We also found that the median PFS（12 months）in Foxp3^high group was significantly longer than the Foxp3^low group（31months,P<0.05）.Median PFS in CD8^high group（25 months）was significantly higher than that of CD8^low group（12 months,P<0.05）.Subgroup analysis showed that the median PFS in Foxp3^high CD8^low group（7 months）was significantly lower than that in the group of Foxp3^highCD8^high（25 months）,Foxp3^lowCD8^high（missing）and Foxp3^lowCD8^low group（18 months）,P=0.003.Univariate analysis showed that the tumor location,the number of Foxp3⁺Tregs,the number of CD8⁺T cells,and distant metastases were the factors affecting the prognosis of patients with malignant melanoma.In the the subgroup of mucosa malignant melanoma,there is negative correlation between numbers of Treg and prognosis,and the number of CD8⁺T cells was positively correlated with prognosis.Conclusion:The number of Tregs was closely associated with progress of malignant melanoma.Compared with cutaneous malignant melanoma,there was more Tregs in the local microenvironment of mucosal malignant melanoma.Our results indicated that the poor prognosis of mucosal malignant melanoma may be associated with the infiltration of more Tregs.The number of CD8⁺T cells the number of CD8⁺T cells and presence of ulceration have significant correlation,there was no significant correlation related with lymph node metastasis,distant metastasis;CD8⁺T cells/Treg have significant correlation with presence of ulceration and distant metastasis.Tregs,CD8⁺T cells were prognostic factors in patients with malignant melanoma,Tregs was related to prognosis of malignant melanoma negatively,and CD8⁺T cell was related to prognosis of malignant melanoma positively.In the the subgroup of mucosa malignant melanoma,there is negative correlation between numbers of Treg and prognosis,and the number of CD8⁺T cells was positively correlated with prognosis.