Search

Myeloid-derived suppressor cells (MDSCs) and tumor associated macrophages (TAMs) play key roles in the tumor immune suppressive network and tumor progression. However, precise roles of programmed death-1 (PD-1) in immunological functions of MDSCs and TAMs in head and neck squamous cell carcinoma (HNSCC) have not been clearly elucidated. In the present study, we show that PD-1 and PD-L1 levels were significantly higher in human HNSCC specimen than in normal oral mucosa. MDSCs and TAMs were characterized in mice and human HNSCC specimen, correlated well with PD-1 and PD-L1 expression. αPD-1 treatment was well tolerated and significantly reduced tumor growth in the HNSCC mouse model along with significant reduction in MDSCs and TAMs in immune organs and tumors. Molecular analysis suggests a reduction in the CD47/SIRPα pathway by PD-1 blockade, which regulates MDSCs, TAMs, dendritic cell as well as effector T cells. Hence, these data identify that PD-1/PD-L1 axis is significantly increased in human and mouse HNSCC. Adoptive αPD-1 immunotherapy may provide a novel therapeutic approach to modulate the micro- and macro-environment in HNSCC.

In this study, we accessed the expression and correlation of p-STAT3 with Survivin, Cyclin D1, CD147, Slug and Ki67 by immunohistochemical staining of human tissue microarray which contains 72 adenoid cystic carcinoma (AdCC), 12 pleomorphic adenoma (PMA) and 18 normal salivary gland (NSG) using digital pathological scanner and scoring system. We found that the expression of p-STAT3, Survivin, Slug, Cyclin D1 and CD147 was significantly increased in AdCC as compared with PMA and (or) NSG (p0.05). Correlation analysis of these proteins revealed that p-STAT3 up-regulates the expression of Survivin, Slug, Cyclin D1 and CD147 (p

Epithelial-mesenchymal transition (EMT) is considered to have pivotal roles in the invasive and metastatic of Adenoid cystic carcinoma (AdCC) which is marked by local infiltration and distant metastasis. Notch signaling abnormity has been implicated as important molecular events in recent next generation sequencing studies of AdCC, but the detail is still unclear. This study was designed to investigate the expression of Notch signaling pathway and its relation with EMT program in AdCC. We constructed custom-made Tissue microarray (TMA) to evaluate the immunoreactivity of Notch signaling and EMT program and found that Notch signaling increase consecutively from NSG, PMA to AdCC, suggesting Notch signaling pathway may be associated with human AdCC progression. Then, we carried out Pearson correlation analysis and showed a close correlation of Notch signaling and EMT progression. When blocking Notch signaling pathway with γ-secretase inhibitor DAPT, EMT progression was decreased and migration and invasion ability were declined. Collectively, these findings suggest the vital roles of Notch signaling pathway in AdCC progression through their relationship with EMT progress. Targeting Notch signaling may provide further understanding of the mechanism of invasion and metastasis of AdCC as well as potential clinical therapeutics.