Uncovering PD-L1 and CD8⁺ TILS Expression and Clinical Implication in Cervical Squamous Cell Carcinoma

Abstract

Objective. To investigate the association between programmed death-ligand 1 (PD-L1) coupled with CD8+ tumor-infiltrating lymphocytes (TILS) and the clinicopathological features, along with prognosis of cervical squamous cell carcinoma (CSCC). Methods. 95 patients of CSCC received tumor resection at the Department of Pathology of the First Affiliated Hospital of University of Science and Technology of China (USTC) from 2015 to 2020. Full-automatic immunohistochemistry was applied to measure PD-L1 expression and CD8+ TILS density. Our literature deeply assessed the links between PD-L1 expression, clinicopathological features, and the influences of combination of PD-L1 and CD8+ TILS (PD-L1+/CD8+ TILS) on the prognosis of CSCC. Results. 64.21% of CSCC patients (61/95) expressed PD-L1, and PD-L1 expression was related to the Federation of Gynecology and Obstetrics (FIGO) stage, tumor size, invasion depth, differentiation degree, metastasis of lymph node, and vascular invasion (P<0.05). Dramatic correlation between PD-L1 expression and CD8+ TILS density was illustrated in CSCC patients (r=−0.461, P<0.001). Obvious differences in differentiation degree, FIGO stage, infiltration depth, and lymph node metastasis were shown between patients with PD-L1 coupled with high-density of CD8+ TILS and those with PD-L1 coupled with low-density of CD8+ TILS (P<0.05). Patients with PD-L1 negative expression exhibited better prognosis compared with those with PD-L1 positive expression (P<0.05). Patients with PD-L1 coupled with high-density of CD8+ TILS showed better prognostic status, while those with PD-L1 coupled with low-density of CD8+ TILS had worse prognostic condition (P<0.05). Differentiation, metastasis of lymph node, and FIGO stage were substantive impact elements of a CSCC patient’s overall survival (OS) by Cox multivariate analysis. Conclusions. CD8+ TILS density is related to PD-L1 expression in carcinoma. PD-L1/CD8+ TILS density can be regarded as evaluation for the prognosis of patients with CSCC, providing a new therapeutic target in clinical application.

An analysis of the immunological tumor microenvironment of primary tumors and regional lymph nodes in squamous cell lung cancer

“…Patients with a high density of CD8+ TILs in tumors showed a better prognosis than those with a low density of cells. The best prognosis for cervical squamous cell carcinoma patients was shown in the high-density PD-L1−/CD8+ TIL group, and the worst prognosis was shown in the low-density PD-L1+/CD8+ TIL group (42). Burrack reported that the PD-L1 expression was associated with the CD8+ TIL density in pancreatic cancer tissue, implying the tumor immune response and immunogenicity of tumors (43).…”

Moesin Serves as Scaffold Protein for PD-L1 in Human Uterine Cervical Squamous Carcinoma Cells

“…Additionally, we also verified the similar results in HCS-2 cells. Many studies in human clinical SCC tissues have revealed that PD-L1, ezrin, and moesin are widely expressed in laryngeal [41][42][43] and oral [44][45][46][47][48][49] SCCs, PD-L1; and that ezrin are expressed in tongue [50][51][52] and esophageal [53][54][55][56][57] SCCs; and that PD-L1 and moesin are expressed in uterine cervix SCC [58][59][60]. In contrast, radixin expression has been reported only in the human tongue SCC cell line Tca8113 [61].…”

“…This is likely, because radixin is a dominant ERM protein in the hepatic tissues and hepatocytes [71]. Given that in contrast to ezrin and radixin, moesin is highly expressed in the human uterine cervix SCC [58][59][60], moesin may regulate the plasma membrane localization of PD-L1 as a predominant ERM protein in BOKU cells and HCS-2 cells, as is the case with ezrin in HeLa and LS180 cells [31,32]. The detailed mechanism by which PD-L1 selects a particular ERM protein as a partner for its plasma membrane localization in several cancer cell types will have to be addressed in future studies.…”

“…Importantly, the expression statuses of moesin and PD-L1 have been associated with poor prognosis, tumor malignancy, and metastasis in patients with uterine cervical SCC [58][59][60]72]. In fact, analysis using the human cervical SCC tissues obtained from TCGA database showed a higher expression of PD-L1 gene in the human cervical SCC tissue and a lower survival rate in the cervical SCC patients who had a higher expression of moesin.…”

Programme death ligand 1 expressions as a surrogate for determining immunotherapy in cervical carcinoma patients

“…This could actually be due to the fact that these type of carcinomas have high density of CD8+ tumour infiltrating lymphocytes (TILs) [ 17 , 18 ]. The presence of prominent TILs in PD-L1 positive cervical carcinomas is associated with longer survival compared to cervical carcinoma patients with low or no TILs [ 19 , 20 ]. Thus, care is needed when interpreting PD-L1 positivity in relation to prognosis, this has led to development and proposition of the immune-score in predicting clinical outcomes in cervical carcinoma [ 21 ].…”