Clinicopathological correlation of PD-L1 and TET1 expression with tumor-infiltrating lymphocytes in non-small cell lung cancer

The immunohistochemical analysis of PD-L1 expression is still important in cancer immunotherapy. PD-L1 expression is affected by various tumor microenvironmental factors including tumor infiltrating lymphocytes (TILs) and DNA methylation biomarkers. Given the complex communication between tumor cells and immune cells, we analyzed the expression of PD-L1 and TET1 with TILs in human NSCLC and the correlation with various clinicopathological characteristics and patient prognosis. A total of 96 cases of NSCLC were enrolled in this study. Using tissue microarray, we performed immunohistochemical staining to analyze PD-L1 and TET1 expression. Image-Pro Plus was used as an automated imaging analysis software program to analyze the density of CD3+, CD4+ and CD8 + TILs. PD-L1 expression was positively correlated with the density of CD3+, CD4+ and CD8 + TILs (p = 0.038, p = 0.020, and p = 0.009, respectively); however, no significant relationship existed between TET1 expression and any TILs. The survival analysis revealed that a high PD-L1 expression was associated with favorable prognosis for OS (p = 0.049) and DFS (p = 0.029) in advanced-stage II-IV patients, but not in early stage I. Density of CD8+ TILs was an independent and favorable prognostic factor for DFS (p = 0.008) and OS (p = 0.002) in early-stage I patients. However, high TET-1 expression was associated with poor prognosis for OS (p = 0.029) in total NSCLC patients. These findings suggest the correlation and favorable prognostic impact of PD -L1 and TILs in NSCLC. In addition, DNA demethylase TET1 has oncogenic effects, showing association with poor prognosis.