Dataset Information

Prognostic Significance of PD-L1 Expression and Its Tumor-Intrinsic Functions in Hypopharyngeal Squamous Cell Carcinoma.

ABSTRACT: Purpose:The expression of programmed death-ligand 1 (PD-L1) is common in various solid human cancers and it is an important therapeutic target. However, the expression pattern, clinical significance and potential mechanism of PD-L1 in hypopharyngeal squamous cell carcinoma (HSCC) are still lacking. Methods:PD-L1 expression in HSCC tumor tissues and paired adjacent hypopharyngeal mucosal tissues was detected using immunohistochemistry assay, and the clinical significance of PD-L1 in HSCC was characterized. In vitro assays including cell viability assays, migration assays, invasion assays as well as Western blot assays were performed to illuminate the biological functions and underlying molecular mechanisms of PD-L1 in HSCC development. Results:PD-L1 expression was detected in HSCC samples but we found no positive expression in matched normal hypopharyngeal mucosal tissues. The levels of PD-L1 expression were significantly correlated with advanced clinical progression and poor patient survival. Multivariable analysis of Cox model showed that PD-L1 expression was an independent predictor for the prognosis of HSCC patients. Functional experiments showed that the ectopic expression of PD-L1 markedly influenced the proliferation, migration and invasion of FaDu cells in vitro. Mechanistically, investigations demonstrated that PD-L1 could promote the epithelial-mesenchymal transition of FaDu cells. Meanwhile, PD-L1 knockdown inhibited, while PD-L1 overexpression activated the Akt-mTOR signaling pathway in FaDu cells. The EMT induced by PD-L1 overexpression could be reversed by the Akt inhibitor. Conclusion:In summary, the expression of PD-L1 can act as a significant biomarker for the adverse clinicopathological features and poor prognosis of patients with HSCC. PD-L1 can promote the proliferation, migration and invasion of FaDu cells and consequently enhance the aggressiveness. Moreover, PD-L1 induces EMT through AKT-mTOR signaling pathway. These suggest that PD-L1 has important tumor-intrinsic functions independent of its immunopathogenic effects.

SUBMITTER: Cui P

PROVIDER: S-EPMC7373417 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Prognostic Significance of PD-L1 Expression and Its Tumor-Intrinsic Functions in Hypopharyngeal Squamous Cell Carcinoma.

Cui Peng P Jing Peihang P Liu Xiuxiu X Xu Wei W

Cancer management and research 20200717

<h4>Purpose</h4>The expression of programmed death-ligand 1 (PD-L1) is common in various solid human cancers and it is an important therapeutic target. However, the expression pattern, clinical significance and potential mechanism of PD-L1 in hypopharyngeal squamous cell carcinoma (HSCC) are still lacking.<h4>Methods</h4>PD-L1 expression in HSCC tumor tissues and paired adjacent hypopharyngeal mucosal tissues was detected using immunohistochemistry assay, and the clinical significance of PD-L1 i ...[more]

PMID: 32765090

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Project description:BackgroundAn increasing number of studies have examined the ability of programmed death-ligand 1 (PD-L1) to function as a marker for tumor prognosis. However, whether PD-L1 expression is a prognostic factor for the poor outcomes in many human cancers remains controversial. This study aims to investigate the prognostic role of PD-L1 expression through a meta-analysis update of 60 studies.MethodsThe studies were identified by searching PubMed, Embase, Google Scholar, and Cochrane Library, and were assessed by further quality evaluation. The pooled hazard ratios (HRs) with 95% confidence intervals (CIs) for total and stratified analyses were calculated to investigate the association between the PD-L1 expression and the overall (OS) and disease-free (DFS) or progression-free survivals (PFS) of cancer patients. Heterogeneity and publication bias were also investigated.ResultsThe results indicated that PD-L1 overexpression can predict a poor OS (HR = 1.58, 95% CI = 1.38-1.81, P <.000) and DFS/PFS (HR = 1.72, 95% CI = 1.26-2.33, P = .001). Subgroup analyses showed that PD-L1 overexpression was significantly related to the poor OS in patients with breast (HR = 1.98, 95% CI = 1.15-3.41, P = .014), urothelial (HR = 2.24, 95% CI = 1.61-3.12, P <.000), renal (HR = 3.30, 95% CI = 2.23-4.86, P <.000), and gastric cancers (HR = 1.56, 95% CI = 1.02-2.37, P = .040). Furthermore, PD-L1 overexpresion was significantly associated with poor DFS/PFS in patients with hepatocellular carcinoma (HCC) (HR = 1.72, 95% CI = 1.21-2.46, P = .003), melanoma (HR = 3.39, 95% CI = 2.02-5.69, P <.000), and renal carcinoma, (HR = 5.04, 95% CI = 2.87-8.86, P <.000). The adverse prognostic impact of PD-L1 was observed in patients of different ethnicities.ConclusionsThe findings of this meta-analysis suggest the correlation of PD-L1 overexpression with worse OS in patients with solid tumors. However, the correlations differed according to tumor types.

Project description:The PD-1 receptor and its ligands PD-L1 and PD-L2 are known to be significantly involved in T-cell regulation. Recent studies suggest that PD-L1 expression in malignant tumors contributes to an immunosuppressive microenvironment and disruption of antitumoral immune response. Drugs targeting this pathway are already tested in clinical trials against several tumor entities with promising results. However, until now comprehensive data with regard to PD-L1 and PD-L2 expression in head and neck squamous cell carcinoma (HNSCC) is still lacking.We assessed PD-L1 and PD-L2 expression via immunohistochemistry in two independent cohorts of 293 HNSCC patients.A significant subset of HNSCC showed high expression levels of PD-L1. Most remarkable, we detected a strong correlation between PD-L1 expression and overall survival time in both HNSCC cohorts. Further, in multivariate cox proportional hazard models, PD-L1 dominates as the strongest prognostic factor of patient's outcome in HNSCC, leaving even tumor stage and distant metastasis behind. Moreover, strong PD-L1 expression was associated with the presence of distant metastases in a subset of cases.In summary, while the significance of PD-L2 in HNSCC seems to minor, we show that PD-L1 expression is common in HNSCC and, more importantly, a both robust and strong prognostic biomarker. In this respect, our results provide hints on further application of therapies targeting the PD-1/PD-L1 pathway in HNSCC. Investigation of response and outcome of patients receiving anti-PD-1/PD-L1 containing therapies in correlation with PD-L1 expression analysis should be an important task for the future.In spite of improved treatment options and increasing knowledge of molecular alterations in HNSCC, the survival rate has not been dramatically changed in the past decades. Pies are missing in HNSCC. One promising candidate in cancer immune therapy is PD-L1. Drugs targeting PD-L1 or its receptor PD-1 are subject of several clinical studies in different cancer entities. However, comprehensive data about PD-L1 expression in HNSCC and therefore a rational basis for anti PD-L1/PD-1 therapy in HNSCC is lacking. Here, we provide wide-ranging data about PD-L1 expression in HNSCC of all major localizations. We observed a strong correlation between expression of PD-L1 and reduced overall survival time. Furthermore, high PD-L1 expression was identified as a strong prognostic factor of patient's outcome when verified together with recognized prognostic factors.

Dataset Information

Prognostic Significance of PD-L1 Expression and Its Tumor-Intrinsic Functions in Hypopharyngeal Squamous Cell Carcinoma.

Publications

Prognostic Significance of PD-L1 Expression and Its Tumor-Intrinsic Functions in Hypopharyngeal Squamous Cell Carcinoma.

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