Expression level of PD-L1 is involved in ALDH1A1-mediated poor prognosis in patients with head and neck squamous cell carcinoma.

To evaluate the expression levels of ALDH1A1, PDL1, and PDL2 in head and neck squamous cell carcinoma (HNSCC) patients, and explore their clinical relevance in prognosis of patients with HNSCC. Immunohistochemistry of ALDH1A1 and PD-L1/PD-L2 in 85 primary HNSCC patients was carried out. The expression level of PD-L2 was assessed with the modified Moratin's immune response scoring (IRS) system. tumor proportion score (TPS) was defined as the percentage of viable tumor cells showing partial or complete membrane staining at any intensity. The chi-square test and Fisher's exact test were used to analyze the associations between ALDH1A1 expression and clinicopathological features. The Spearman's correlation was applied to analyze the correlation of ALDH1A1 expression with PD-L1/PD-L2 expression. kaplan-Meier analysis showed that the expression levels of ALDH1A1 and PD-L1/PD-L2 were inversely associated with recurrence-free survival (RFS; P = 0.001, 0.014, and 0.023, respectively). Moreover, expression levels of ALDH1A1 and PD-L1 were correlated with poor overall survival (OS; P = 0.002 and 0.039, respectively). Furthermore, multivariate logistics regression analyses demonstrated that expression level of ALDH1A1 was independently associated with shorter RFS (P = 0.013) and poorer OS (P = 0.014) in HNSCC patients, and the expression level of PD-L2 was only negatively associated with RFS (P = 0.041), rather than PD-L1. Spearman's correlation analysis unveiled that expression levels of PD-L1 and PD-L2 were positively correlated with ALDH1A1 expression in HNSCC patients (P = 0.000 and 0.015, respectively). Especially, the patients with expression levels of ALDH1A1 and PD-L1 had the worst prognosis. Our results indicated that ALDH1A1 is an independent prognostic factor in patients with HNSCC, and the expression level of PDL-1 may be involved in ALDH1A1-mediated poor prognosis in patients with HNSCC.

Zhou AL ，Wang X ，Yu W ，Yang L ，Wei F ，Sun Q ，Wang Y ，Kou F ，Dong R ，Ren X ，Zhang X ... -  《-》

Expression of PD-1/PD-L1 in head and neck squamous cell carcinoma and its clinical significance.

Chen SW ，Li SH ，Shi DB ，Jiang WM ，Song M ，Yang AK ，Li YD ，Bei JX ，Chen WK ，Zhang Q ... -  《-》

Assessment of cancer stem cell marker expression in primary head and neck squamous cell carcinoma shows prognostic value for aldehyde dehydrogenase (ALDH1A1).

Cancer stem cells (CSCs) play a key role in carcinogenesis and progression of head and neck squamous cell carcinomas (HNSCC). The most common markers indicating for CSCs are: CD44, CD24, CD133, ALDH1A1. Our objective was to evaluate the prognostic potential of CSC markers in HNSCC. The study included 49 patients treated for primary HNSCC, 11 patients with upper respiratory tract epithelial dysplasia and 12 subjects with the normal pharyngeal mucosa as a control group. The frequency and expression levels of the four CSC markers were assessed by immunohistochemistry. Univariate and multivariate analyses were used to correlate CSC expression levels with tumor stage, lymph node metastases or overall survival (OS). CD44, CD24, CD133, ALDH1A1 were widely expressed in tumors, whereas CD44 was found to be higher in cancer tissue (P = 0.001). ALDH1A1 expression levels were found to be significantly higher in T3-T4 tumors vs. T1-T2 tumors (P = 0.05). Lymph node metastases had significantly higher expression levels of CD24 (P = 0.01) and CD133 (P < 0.05) than primary tumors. Multifactorial analysis revealed that overall survival (OS) for patients with ALDH1A1 negative tumors was 5.25 times higher than for patients with ALDH1A1 positive (ALDH1A1+) tumors (P = 0.01). On univariate and multivariate analysis, only ALDH1A1 positivity had a significant effect on OS of HNSCC patients (HR = 2.47 for P = 0.02). Immunohistochemistry-based assessments of CSC marker expression in HNSCC has significant predictive implications for patients with HNSCC. The frequency of CSCs in the tumor, specifically of ALDH1A1+ cells correlated with five-year OS in these patients.

Szafarowski T ，Sierdziński J ，Ludwig N ，Głuszko A ，Filipowska A ，Szczepański MJ ... -  《-》

The prognostic role of PD-L1 expression for survival in head and neck squamous cell carcinoma: A systematic review and meta-analysis.

Programmed death-ligand 1 (PD-L1) is an immune checkpoint that is primarily located on the surface of tumor cells. PD-L1 expression detected by immunohistochemistry (IHC) assays has been widely studied to predict survival outcomes in head and neck squamous cell carcinoma (HNSCC) recently. We aimed to review comprehensively the prognostic role of PD-L1 expression for survival in HNSCC. We systematically searched PubMed, Embase, Web of Science, Cochrane Library and Scopus to identify studies investigating the prognostic role of PD-L1 expression in HNSCC. All studies published before March 31, 2018 were screened. Included studies were assessed using the Quality in Prognosis Studies (QUIPS) tool. Data were extracted and overall survival (OS), disease-free survival (DFS), progression-free survival (PFS), disease-specific survival (DSS) were combined and presented as hazard ratios (HR) with 95% confidence interval (CI) using the generic inverse-variance method. Twenty-three studies with 3105 patients were analysed. The overall positive rate of PD-L1 in HNSCC was 0.42 (95% CI: 0.36-0.48). There was no significant difference between PD-L1-positive and -negative HNSCC patients in OS (HR: 0.98; 95% CI: 0.71-1.37; p = 0.93), DFS (HR: 1.07; 95% CI: 0.68-1.70; p = 0.76), and DSS (HR: 0.90; 95% CI: 0.63-1.29; p = 0.56). An improved PFS was observed in patients with positive PD-L1 expression (HR: 0.71; 95% CI: 0.55-0.93; p = 0.01). In patients with low CD8+ tumor-infiltrating T cells, a poorer OS was detected in patients with positive PD-L1 expression (HR: 1.90; 95% CI: 1.07-3.36; p = 0.03). Patients with HPV-positive HNSCC were associated with increased PD-L1 expression (OR: 1.99; 95% CI: 1.50-2.64; p < 0.001). However, PD-L1 expression showed no significant benefit on OS in HPV-positive HNSCC (HR: 1.04; 95% CI: 0.65-1.65; p = 0.88). PD-L1 expression detected by IHC was not recommended to predict survival in HNSCC patients. However, the positive PD-L1 expression might predict better PFS in patients with advanced HNSCC. The combined effects of PD-L1 expression and CD8+ tumor-infiltrating T cells should be further elucidated.

Yang WF ，Wong MCM ，Thomson PJ ，Li KY ，Su YX ... -  《-》

PD-L1 expression correlates with tumor-infiltrating lymphocytes and better prognosis in patients with HPV-negative head and neck squamous cell carcinomas.

Sanchez-Canteli M ，Granda-Díaz R ，Del Rio-Ibisate N ，Allonca E ，López-Alvarez F ，Agorreta J ，Garmendia I ，Montuenga LM ，García-Pedrero JM ，Rodrigo JP ... -  《-》