Immunohistochemically evaluation of CD4, CD8, FOXP3 expressions in pancreatic adenocarcinomas and comparison with prognostic parameters

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive and early metastatic tumor that is one of the leading causes of cancer-related death. In addition, PDAC is among the most resistant cancers to chemotherapy and radiotherapy. Only surgical treatment is recommended as a cure chance. PDACs have intense stromal fibrosis and there is intense inflammation involving Treg cells and CD4+ or CD8+ T cells in the tumor microenvironment. Treg cells are identified by the expression of FOXP3, but FOXP3 expression can be transiently induced in activated cells (such as CD8+ T cells, activated CD4+ T cells). Generally, FOXP3+ Treg cells exert suppressive / anti-inflammatory functions through a number of mechanisms. Today, it is believed that Treg cells play an important role in preventing immunity against cancer. However, it is thought that the ratio of CD4+ and CD8+ T cells, which are among the other elements of the tumor microenvironment, in PDACs may be related to the advanced prognosis. If the prognostic importance of FOXP3+ cells in the tumor microenvironment, the amount/presence of CD4+ FOXP3+ cells and CD8+ FOXP3+ cells in them, and the ratio of CD4+ and CD8+ T cells in the tumor microenvironment can be understood, treatment approaches targeting them can be developed. In this study, it was aimed to evaluate the CD4, CD8, FOXP3 expressions in the tumor microenvironment in pancreatic adenocarcinomas immunohistochemically and to investigate the relationship with other prognostic parameters. For our study, tumor blocks of the resection materials of 50 cases operated for PDAC in our center between 01.01.2013-31.12.2018 were used. FOXP3-CD4 antibodies and FOXP3-CD8 antibodies were applied to these cases by immunohistochemical double staining method. Staining results were evaluated under a light microscope. These data and the ratios obtained from these data were used in the statistical evaluation. Compliance of the obtained data to normal distribution, comparison of the mean of independent groups, percentage distribution of categorical data between groups, correlation of more than one continuous data were calculated using SPSS v20. In PDACs, it was observed that as the amount of FOXP3 + cells in the tumor increased, the degree of differentiation of the tumor decreased, and the differentiation degree of the tumor decreased with the presence of CD8+ FOXP3+ cells. There was no relationship between the amount/presence of CD8+ FOXP3+ cells, the amount of CD4+ FOXP3+ cells and the ratio of CD4+/CD8+ T cells and the diameter, differentiation, stage, lymphovascular invasion, perineural invasion, lymph node metastasis, surgical margin and surrounding tissue invasion. It was observed that the amount of CD4+ FOXP3+ cells in FOXP3+ cells was greater than the amount of CD8+ FOXP3+ cells. Although there are cases without CD8 + FOXP3 + cells, there are no cases without CD4 + FOXP3 + cells. There is also a moderate linear correlation between the amount of FOXP3+ cells and the amount of CD8+ FOXP3+ cells, and a high level of linear correlation between the amount of FOXP3+ cells and the amount of CD4+ FOXP3+ cells. There was no correlation with the CD4+ / CD8+ T cell ratio.