<p>Prognostic Significance of PD-L1 Expression and Its Tumor-Intrinsic Functions in Hypopharyngeal Squamous Cell Carcinoma</p>

Abstract

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 epithelialmesenchymal 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.

Development and validation of a nomogram to predict cancer-specific survival in patients with hypopharyngeal squamous cell carcinoma treated with primary surgery

“…23,24 Second, the predictive Recently, studies have shown that gene patterns, PD-L1, and the immune microenvironment can also reflect the prognosis of HSCC. [25][26][27] Thus, a multi-omics model should be developed in the future to improve the predictive accuracy of prognosis in these patients. Third, the present nomogram was developed based on a retrospective population-based analysis, which was not externally validated.…”

HOXA11-AS1 Promotes PD-L1 Mediated Immune Escape and Metastasis of Hypopharyngeal Carcinoma by Facilitating the Association of PTBP1 with FOSL1

“…In addition, since PD-L1 is often reported to be overexpressed in malignant tumors, mechanically, helps cancer cells evade recognition by the host immune system, PD-L1 has also become the focus of oncologic research (26,27). Previous studies have reported the immunopathogenic effect and cancer-intrinsic function of PD-L1 in HSCC (11,28), however, in general, the contributions of PD-L1 in the pathogenesis still need more discussion. In this study, we found that knockdown of HOXA11-AS1 suppressed immune escape and metastasis in HSCC through down-regulating PD-L1 levels by inhibiting the interaction between FOSL1 and PTBP1.…”

“…For example, Wintterle et al suggested that PD-L1 modulated CD4+ and CD8+ T cell levels by increasing cytokine concentration, such as IFN-γ, thus showing immunomodulatory function in glioma cells (9). Similarly, the high expression of PD-L1 facilitated HSCC cells to escape recognition of the host immune system and accelerated the tumor metastasis (10,11), indicating that the inhibition of PD-L1 might has positive effect for HSCC treatment. However, the speci c function mechanism of PD-L1 needs more investigation.…”

Increased PD-L1 and p16 Expression are Common in Oropharyngeal Squamous Cell Carcinoma

“…Our analysis demonstrated that PD-L1 expression was high in hypopharyngeal carcinoma. There are data to suggest that overexpression of PD-L1 can act as a significant biomarker for the adverse clinicopathologic features and poor prognosis of patients with hypopharyngeal squamous cell carcinoma [ 25 ]. Our study reported that PD-L1 expression was high in three out of four patients with laryngeal squamous cell carcinoma.…”