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Tertiary lymphoid structures (TLSs) are formed in long‐term chronic inflammation, promoting the local recruitment of lymphocytes, antigen presentation and regulation of immune response, correlated with a better prognosis for cancer patients. Although studies have been conducted to explore methods that accelerate the establishment of TLSs, related research in head and neck squamous cell carcinoma (HNSCC) is still lacking. In this study, we analysed data from The Cancer Genome Atlas and performed immunohistochemical staining analyses of 188 patient samples. The results showed that TLSs promoted the infiltration of immune cells. Patients with TLSs with high infiltration of CD8+ cells showed the best prognosis. Since lymphotoxin α (LTα) was significantly increased in tissues with TLSs, we overexpressed LTα in SCC7 cells (a mouse‐derived HNSCC cell line) and established tongue‐tumour‐bearing models. The polychromatic observation of tissue sections showed that T‐cell aggregation increased in the LTα cell group, and a grade 1 TLS was formed on the 12th day after inoculating the cells. Moreover, the tumour volume in the LTα group was significantly less than that of the control group, whereas both the number and the proportion of infiltrated CD8+ T cells were increased. The peripheral CD8+ cells in mice were removed, and no difference was observed in tumour size or TLS formation. Remarkably, we found that TLS led to an increase in the antitumour effect by recruiting CD8+ T cells in HNSCC, showing a CD8+ T‐cell‐dependent antitumour effect. Moreover, LTα overexpression in the tumour promoted the formation of TLSs. [ABSTRACT FROM AUTHOR]

N6-methyladenosine (m6A) is a form of posttranscriptional modification that plays important roles in cancer including oral squamous cell carcinoma (OSCC). Most studies to date have focused on a limited number of regulators and oncogenic pathways, thus failing to provide comprehensive insight into the dynamic effects of m6A modification. In addition, the role of m6A modification in shaping immune cell infiltration in OSCC has yet to be clarified. This study was designed to assess m6A modification dynamics in OSCC and to understand how such modifications influence clinical immunotherapeutic treatment outcomes. m6A modification patterns linked with 23 m6A regulators were analyzed in 437 OSCC patients from TCGA and GEO cohorts. These patterns were then quantified through m6A score based on algorithms derived from a principal component analysis (PCA) approach. The m6A modification patterns of OSCC samples were grouped into two clusters based on the m6A regulators expression, and immune cell infiltration was linked with the 5-year survival outcomes of patients in these clusters. 1575 genes associated with OSCC patient prognosis were identified and used to re-cluster these samples into two groups. Patients in clusters exhibiting higher levels of m6A regulator expression exhibited poorer overall survival (OS), whereas patients with high m6A scores survived for longer (p < 0.001). The overall mortality rates in the groups of patients with low and high m6A scores were 55% and 40%, respectively, and the m6A score distributions in clusters of patients grouped by m6A modification patterns and gene expression further supported the link between a high m6A score and better prognostic outcomes. Immunophenoscore (IPS) values for patients in different m6A score groups suggested that the use of PD-1-specific antibodies or CTLA-4 inhibitors alone or in combination would yield superior treatment outcomes in patients in the high-m6A score group relative to the low-m6A score group. m6A modification patterns are relevant to heterogeneity in OSCC. Detailed analyses of m6A modification patterns may thus offer novel insight regarding immune cell infiltration within the OSCC tumor microenvironment, guiding novel efforts to provide patients with more effective immunotherapeutic interventions. [ABSTRACT FROM AUTHOR]

Background: miRNAs and mRNAs have been significantly implicated in tumorigenesis and served as promising prognostic biomarkers for human cancer. Hence, this study was aimed to develop the pivotal miRNA biomarkers‐based prognostic signature for salivary adenoid cystic carcinoma. Methods: The miRNA and mRNA expression data were integrated from the gene expression omnibus database to study their involvement in salivary adenoid cystic carcinoma development and progression. Gene ontology and kyoto encyclopedia of genes and genomes were conducted to analyze the biological pathways. Reverse transcription‑quantitative PCR was used to verify the expression of selected miRNAs in salivary adenoid cystic carcinoma and corresponding normal tissues. Results: There were 386 differentially expressed genes: 158 upregulated and 228 downregulated genes and 102 differentially expressed miRNAs: 78 upregulated and 24 downregulated miRNAs in the salivary adenoid cystic carcinoma samples. A miRNA‐mRNA network containing 11 miRNAs and 199 genes was subsequently constructed. Gene ontology and Kyoto encyclopedia of genes and genomes enrichment analysis revealed that the genes targeted by the 11 miRNAs were mostly involved in tumor‐related pathways and processes, such as miRNAs in cancer, focal adhesion, neurotrophin signaling pathway, and the PI3K‐Akt signaling pathway. Among them, 4 miRNAs (miR‐375, miR‐494, miR‐34c‐5p, and miR‐331‐3p) were selected to verify by reverse transcription‑quantitative PCR in 36 pairs of collected salivary adenoid cystic carcinoma and adjacent nontumor samples. Overall survival analysis revealed that the higher expression of miR‐331‐3p was significantly associated with a worst overall survival and multivariate Cox regression analysis suggested that hsa‐miR‐331‐3p could be an independent prognostic factor for salivary adenoid cystic carcinoma. Conclusion: Our results revealed that 4‐miRNAs signature was a powerful prognostic biomarker for salivary adenoid cystic carcinoma, which provide a basis for exploring deeper mechanisms regarding the progression of salivary adenoid cystic carcinoma, and leading to the development of potential therapeutic strategies. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to develop a nomogram to predict the neck occult metastasis in early (T1‐T2 cN0) oral squamous cell carcinoma (OSCC). Materials and Methods: The nomogram was developed in a training cohort of 336 early OSCC patients and was validated in a validation cohort including 88 patients. Independent predictors were calculated by univariate and multivariate logistic regression analyses. Results: In univariate logistical regression analysis, gender, perineural invasion (PNI), blood vessel invasion, mean corpuscular hemoglobin, aspartate aminotransferase, prealbumin, globulin (GLO), lactate dehydrogenase (LDH), serum sodium (NA), and serum chloride were significant associated with neck occult metastasis. Multivariate logistical regression analysis identified PNI (p <.001), LDH (p =.003), GLO (p =.019), and NA (p =.020) as independent predictors of neck occult metastasis. Cut‐off values for LDH, GLO, and NA obtained from AUC were 142.5, 26.35, and 139.5, respectively. The nomogram based on PNI and categorical GLO, LDH, and NA exhibited a strong discrimination, with a C‐indexes of 0.748 (95%CI = 0.688 to 0.810) in the training cohort and 0.751 (95%CI = 0.639 to 0.863) in the validation cohort. Conclusions: A nomogram based on PNI, LDH, GLO, and NA for predicting the risk of neck lymph nodes occult metastasis in OSCC could help surgeons with therapy decision‐making. [ABSTRACT FROM AUTHOR]