PD-L1 Expression Correlates With Young Age and CD8+ TIL Density in Poorly Differentiated Cervical Squamous Cell Carcinoma.

Abstract

Management options are limited in advanced or recurrent cervical carcinoma. The Food and Drug Administration has recently approved programed cell death-1 (PD-1)/PD-ligand-1 (PD-L1) inhibitors for the treatment of advanced PD-L1 positive cervical cancer. We studied PD-L1 expression in cervical squamous cell carcinoma (CSCC) samples initially on a The tissue microarray and then in full-tissue sections from poorly differentiated (grade 3) cancers. Tissue microarray was composed of 45 grade 3 and 2 (moderately differentiated) tumors. PD-L1 expression was evaluated as categorical data and by obtaining combined positive score of neoplastic and mononuclear inflammatory cells. In tissue microarray samples PD-L1 expression was higher in poorly differentiated cancers compared with grade 2 tumors by immunohistochemistry. Full-tissue sections from grade 3 CSCC (n=22) were stained with PD-L1, CD8, and VEGF antibodies. Poorly differentiated CSCC samples had diffuse (≥50%) and focal/patchy staining patterns. The latter pattern showed localized tumor-stroma interface staining in 5 samples with low combined positive score. Importantly, younger patients (median=36) had tumors with higher expression. PD-L1 expression was associated with larger tumor size and absent lymphovascular invasion. In addition, CD8 tumor-infiltrating lymphocyte density within the neoplastic tissue matched with PD-L1 levels. The overall survival rates did not correlate with PD-L1 expression. However, in early-stage disease high CD8 tumor-infiltrating lymphocyte density within the peritumoral stroma was associated with better survival outcomes in multivariate analysis. PD-L1 expression and CD8 tumor-infiltrating lymphocyte density may be useful to define a subgroup of patients with relatively better prognosis in poorly differentiated CSCC. It is warranted to validate our results in a larger sample size.