Epithelial PD‐L1 expression at tumor front predicts overall survival in a cohort of oral squamous cell carcinomas from Sudan

Abstract

Background We recently described the tumor immune microenvironment (TIME) in oral squamous cell carcinomas (OSCC) from Sudan by assessing the core of the lesions. However, the invasive tumor front (ITF) is the most active part of OSCC lesions; thus, TIME should also be characterized at the ITF in this patient cohort. Objectives We aimed to evaluate patterns of immune cell infiltration at the ITF in a cohort of OSCC patients from Sudan previously investigated at the tumor center and their association with clinicopathological parameters. Methods This study was performed on a prospective cohort of 22 OSCC patients attending Khartoum Dental Teaching Hospital with a median follow‐up of 48 months. Inflammatory infiltrate densities of CD4‐, CD8‐, FoxP3‐, CD20‐, CD66b‐, M1 (CD80/CD68)‐, M2 (CD163/CD68)‐, and PD‐L1‐positive cells were assessed at the ITF by immunohistochemistry, followed by digital quantitative analysis at the stromal and epithelial compartments separately. Histopathological parameters such as the worst pattern of invasion, differentiation, and tumor budding (TB) were also assessed. Correlations between clinicopathological parameters and survival analysis were investigated using SPSS. Results All inflammatory cell subsets investigated were found to be higher in the stromal compartment as compared to the epithelial one, except for the PD‐L1+ subset. Stromal infiltration with the CD8+ cell subset was associated with low TB. Kaplan–Meier analyses identified higher epithelial and stromal CD4+ cell subsets. The presence of PD‐L1 was found to be associated with unfavorable overall survival. Further, Cox's regression analysis using an age‐ and tumor‐stage‐adjusted model identified epithelial PD‐L1 expression at the ITF as the only independent prognosticator. Conclusions Epithelial PD‐L1 expression at the ITF was found to be an independent prognostic biomarker for OSCC in a cohort of Sudanese patients.

Prognostic Role of Tumor-Infiltrating Lymphocytes in Oral Squamous Cell Carcinoma

“…However, 2 studies have reported findings that contradict our findings. Spector et al and Gaafar et al, reported that higher CD4 + cell counts were associated with advanced-stage OSCC [ 41 , 46 ]. Additionally, the study by Gaafar et al found that dense CD4 + cell infiltrate was associated with poorly differentiated tumors.…”

“…For example, Sales de Sa et al found that increased CD4 + expression tended to have a worse prognosis in OSCC, but this result was not significant and the study only included 48 participants [ 37 ]. Gaafar et al found that dense CD4 + cells were associated with worse OS, although it is important to note that the median follow-up time for the study was relatively short (48 months), and the sample size was relatively small ( n = 22) [ 46 ]. At this time, we are unclear about these inconsistent CD4 expression results in OSCCs, however CD4 + cells are able to differentiate into different subsets such as Th1, Th2, Th9, Th17, Th22, Tregs, and Tfh (follicular helper T cells) which all have different roles.…”