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Association between PD-L1 expression combined with tumor-infiltrating lymphocytes and the prognosis of patients with advanced hypopharyngeal squamous cell carcinoma.

ABSTRACT: Limited information is available regarding the immune-related prognostic factors of patients with advanced hypopharyngeal squamous cell carcinoma (HPSCC). The expression of programmed cell death-ligand 1 (PD-L1) in tumor cells contributes to a mechanism that allows cancer cells to escape immune surveillance. We investigated whether PD-L1 or human leukocyte antigen (HLA) class I expression in tumor cells and the tumor-infiltrating lymphocyte (TIL) density were associated with the tumor response to neoadjuvant chemotherapy (NAC) and survival in patients with advanced HPSCC. We retrospectively reviewed 83 consecutive patients with stage III or IV HPSCC who received NAC. We evaluated PD-L1 and HLA class I expression and TIL density using immunohistochemistry. Univariate and multivariate analyses demonstrated that CD8+ TIL density was an independent and significant predictive factor for the response to NAC, progression-free survival (PFS) and overall survival (OS), whereas PD-L1 or HLA class I expression did not significantly correlate. The subgroup analysis revealed that a higher CD8+ TIL density without detectable PD-L1 expression tended to be associated with longer patient survival. These results suggest that PD-L1 expression levels combined with CD8+ TIL density may serve as a predictive biomarker for patients with stage III or IV HPSCC receiving NAC.

SUBMITTER: Ono T

PROVIDER: S-EPMC5696215 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

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Association between PD-L1 expression combined with tumor-infiltrating lymphocytes and the prognosis of patients with advanced hypopharyngeal squamous cell carcinoma.

Ono Takeharu T Azuma Koichi K Kawahara Akihiko A Sasada Tetsuro T Hattori Satoshi S Sato Fumihiko F Shin Buichiro B Chitose Shun-Ich SI Akiba Jun J Hirohito Umeno U

Oncotarget 20171006 54

Limited information is available regarding the immune-related prognostic factors of patients with advanced hypopharyngeal squamous cell carcinoma (HPSCC). The expression of programmed cell death-ligand 1 (PD-L1) in tumor cells contributes to a mechanism that allows cancer cells to escape immune surveillance. We investigated whether PD-L1 or human leukocyte antigen (HLA) class I expression in tumor cells and the tumor-infiltrating lymphocyte (TIL) density were associated with the tumor response t ...[more]

PMID: 29190949

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Project description: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.

Dataset Information

Association between PD-L1 expression combined with tumor-infiltrating lymphocytes and the prognosis of patients with advanced hypopharyngeal squamous cell carcinoma.

Publications

Association between PD-L1 expression combined with tumor-infiltrating lymphocytes and the prognosis of patients with advanced hypopharyngeal squamous cell carcinoma.

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