Squamous cell carcinoma is seen as principal malignancy of head and neck. Tumor immune microenvironment plays a vital role in the occurrence, development and treatment of head and neck squamous cell carcinoma (HNSCC). The effect of immunotherapy, in particular, is closely related to tumor immune microenvironment. This review searched for high-quality literature included within PubMed, Web of Science, and Scopus using the keywords “head and neck cancers,” “tumor microenvironment” and “immunotherapy,” with the view to summarizing the characteristics of HNSCC immune microenvironment and how various subsets of immune cells promote tumorigenesis. At the same time, based on the favorable prospects of immunotherapy having been shown currently, the study is committed to pinpointing the latest progress of HNSCC immunotherapy, which is of great significance in not only further guiding the diagnosis and treatment of HNSCC, but also conducting its prognostic judgement.

Cystatin E/M (CST6), a representative cysteine protease inhibitor, plays both tumor-promoting and tumor-suppressing functions and is pursued as an epigenetically therapeutic target in special cancer types. However, a comprehensive and systematic analysis for CST6 in pan-cancer level is still lacking. In the present study, we explored the expression pattern of CST6 in multiple cancer types across ∼10,000 samples from TCGA (The Cancer Genome Atlas) and ∼8,000 samples from MMDs (Merged Microarray-acquired Datasets). We found that the dynamic expression alteration of CST6 was consistent with dual function in different types of cancer. In addition, we observed that the expression of CST6 was globally regulated by the DNA methylation in its promoter region. CST6 expression was positively correlated with the epithelial cell infiltration involved in epithelial-to-mesenchymal transition (EMT) and proliferation. The relationship between CST6 and tumor microenvironment was also explored. In particular, we found that CST6 serves a protective function in the process of melanoma metastasis. Finally, the clinical association analysis further revealed the dual function of CST6 in cancer, and a combination of the epithelial cell infiltration and CST6 expression could predict the prognosis for SKCM patients. In summary, this first CST6 pan-cancer study improves the understanding of the dual functional effects on CST6 in different types of human cancer.

The aim of this study was to explore the regulatory role of epoxide hydrolase 3 (EPHX3) in head and neck squamous cell carcinoma (HNSCC) and to analyze its bioinformatic function, as well as, to screen and predict the miRNAs that can regulate EPHX3 expression in HNSCC. We examined the expression profile and prognostic potential of EPHX3 in TCGA and GTEX databases and performed functional enrichment analysis of EPHX3 using string database. Subsequently, we analyzed the regulatory role of miRNAs on EPHX3, including expression analysis, correlation analysis, and survival analysis. In addition, we also used TIMER to investigate the relationship among EPHX3 expression level, immune checkpoints, and immune infiltration in HNSCC. The results of data analysis after TGCA showed that EPHX3 is a key regulator of tumorigenesis in 13 cancers and can be used as a marker of poor prognosis in HNSCC patients. Bioinformatics analysis revealed that miR-4713-3p is a key miRNA of EPHX3 in HNSCC. Together, our findings indicate that EPHX3 exerts its anticancer effects by suppressing tumor immune checkpoint expression and immune cell infiltration. Overall, our data uncovered miRNA-mediated EPHX3 downregulation as a contributor to poor HNSCC prognosis and reduced tumor immune infiltration.

Chronic rhinosinusitis (CRS) is a complex condition brought on for many reasons, and its prevalence is rising gradually around the world. Xanthii Fructus (XF) has been used in the treatment of CRS for decades and is effective. The chemical and pharmacological profiles of XF, on the other hand, are still unknown and need to be clarified. The potential mechanisms of XF in CRS treatment were investigated using a network pharmacology approach in this study. OB and DL were in charge of screening the bioactive components in XF and drug-likeness. TCMSP and PubChem databases were used to identify prospective XF proteins, whereas GeneCards and the DisGeNET database were used to identify potential CRS genes. An interactive network of XF and CRS is built using the STRING database based on common goals identified by the online tool Venny. Cytoscape was used to visualize the topological characteristics of nodes, while the biological function pathways were identified by GO Knowledge Base, KEGG. There were 26 bioactive components and 115 potential targets in XF that bind to CRS or are considered therapeutically relevant. Five significant signaling pathways have been found for CRS by the pathway analysis including the HIF-1 signaling pathway, TNF signaling pathway, Toll-like receptor signaling pathway, NOD-like receptor signaling pathway, and PI3K-Akt signaling pathway. We simultaneously confirmed that the PI3K-Akt pathway promotes the development of CRS. Finally, this study took a holistic approach to the pharmacological actions and molecular mechanisms of XF in the treatment of CRS. TNF, INS, CCL2, CXCL8, IL-10, VEGFA, and IL-6 have all been identified as potential targets for anti-inflammatory and immune-boosting effects. This network pharmacology prediction could be useful in manifesting the molecular mechanisms of the Chinese herbal compound XF for CRS.

To investigate the effect of Yupingfeng on hyaluronic acid (HA) and Foxp3(+) Treg in patients with nasopharyngeal carcinoma. A total of 58 cases of nasopharyngeal carcinoma were divided into two groups, 30 cases in the treatment group, 28 cases in the control group. Patients in two groups were treated with synchronous radiotherapy and chemotherapy treatment, the treatment group was treated with the Yupingfeng granules through oral administration, 10 g/time, tid for 2 courses. The serum Foxp3(+) Treg markers of each group were detected by flow cytometry assay before treatment and after treatment, and the level of HA in serum was detected by radio immunoassay. After radiotherapy and chemotherapy, the contents of Foxp3(+) Treg and HA were significantly decreased in two groups (P < 0.05), and the decrease of treatment group was more significantly (P < 0.01). Correlation analysis showed positive correlation between Foxp3(+) Treg and HA (P < 0.05). After treatment, the incidence of side effects in two groups was significantly decreased. And there was significant difference between two groups (P < 0.05). Combined chemotherapy and radiotherapy with Yupingfeng treatment can decrease the levels of Foxp3(+) Treg and HA in nasopharyngeal carcinoma patients. Yupingfeng can also effectively reduce the side effect due to radiation and chemotherapy.