The programmed cell death protein-1 (PD-1)/programmed cell death ligand-1 (PD-L1) axis blockade has been implemented in advanced-stage tumor therapy for various entities, including head and neck squamous cell carcinoma (HNSCC). Despite a promising tumor response in a subgroup of HNSCC patients, the majority suffer from disease progression. PD-L1 is known to influence several intrinsic mechanisms in cancer cells, such as proliferation, apoptosis, migration and invasion. Here, we modulated PD-L1 expression in three HNSCC cell lines with differential intrinsic PD-L1 expression. In addition to an alteration in the epithelial-to-mesenchymal transition (EMT) marker expression, we observed PD-L1-dependent cell spreading, migration and invasion in a spheroid spreading assay on four different coatings (poly-L-lysine, collagen type I, fibronectin and Matrigel^®) and a chemotactic transwell migration/invasion assay. Furthermore, the overexpression of PD-L1 led to increased gene expression and small interfering ribonucleic acid (siRNA) knockdown and decreased gene expression of Rho-GTPases and related proteins in a RT² Profiler™ PCR Array. Rac1 and Rho-GTPase pulldown assays revealed a change in the activation state concordantly with PD-L1 expression. In summary, our results suggest a major role for PD-L1 in favoring cell motility, including cell spreading, migration and invasion. This is presumably caused by altered N-cadherin expression and changes in the activation states of small Rho-GTPases Rho and Rac1.

The aim of this study was to investigate the clinical, histopathologic, and immunologic differences of oral squamous cell carcinoma of never-smokers/never-drinkers and smokers/drinkers. Immunohistochemical staining for CD4, CD8, FoxP3, CD1a, and p16 was performed in 131 oral squamous cell carcinomas from smokers/drinkers and never-smokers/never-drinkers. Associations of smoking/drinking status with clinicopathologic data, immunohistochemical antibody expression, and survival were examined. Oral squamous cell carcinoma in never-smokers/never-drinkers was associated with the female gender (p < 0.001). Never-smokers/never-drinkers were older at diagnosis than smokers/drinkers (p < 0.001). Never-smokers/never-drinkers had more tumors in the maxilla, mandible, and tongue (p < 0.001). Pre-existing oral potentially malignant disorders appeared to be more common in never-smokers/never-drinkers (p < 0.001). Perineural invasion was more common in smokers/drinkers (p = 0.039). Never-smoking/never-drinking was associated with better overall survival (p = 0.004) and disease-specific survival (p = 0.029). High CD4+ T cell infiltration was associated with never-smoking/never-drinking (p = 0.008). Never-smokers/never-drinkers also showed increased CD8+ T cell infiltration (p = 0.001) and increased FoxP3+ Treg infiltration (p = 0.023). Furthermore, the total group of tumor-infiltrating lymphocytes was associated with never smoking/never drinking (p = 0.005). To conclude oral squamous cell carcinoma of the never-smokers/never-drinkers appears to be a distinct type of tumor, as it appears to have unique clinical and pathologic features and a more immunogenic microenvironment.

The treatment of bite wounds to the face is discussed controversially in relation to surgery and antibiotics. The aim of this study is a retrospective evaluation of 111 cases of animal bite injuries to the face that presented to our unit of oral and maxillofacial surgery over a 13-year period. Children under 10 years of age were predominantly involved. A total of 94.5% of the assessed injuries were caused by dogs. Wound infections occurred in 8.1%. Lackmann type II was the most common type of injury (36.9%). The perioral area was affected most frequently (40.5%). Primary wound closure was carried out in 74.8% of the cases. In 91.9% of the cases, antibiotic prophylaxis was prescribed. The most often administered type of antibiotic was amoxicillin with clavulanic acid (62.1%). Patients without antibiotics showed an increased infection rate without significance. Wound infections occurred significantly more frequently in wounds to the cheeks (p = 0.003) and when local flap reconstruction was necessary (p = 0.048). Compared to the other surgical treatment options, primary closure showed the lowest infection rates (4.8%, p = 0.029). We recommend antibiotic prophylaxis using amoxicillin with clavulanic acid and wound drains for wounds of Lackmann class II or higher. Primary closure seems to be the treatment of choice whenever possible.

(1) Background: T-cell immunoglobulin and ITIM domain (TIGIT) is a potential immunotherapeutic target in a variety of malignant entities, and antibody-based treatments are currently under investigation in clinical trials. While promising results were observed in patients with lung cancer, the role of TIGIT in oral squamous cell carcinoma (OSCC) as a biomarker as well as a therapeutic target remains elusive. Therefore, we evaluated the role of TIGIT as a prognostic factor in OSCC. (2) Methods: Here, we describe the results of a retrospective tissue microarray (TMA) OSCC cohort. Using immunohistochemistry, TIGIT expression was correlated with overall and recurrence-free survival (OAS and RFS, respectively). Additionally, in silico analysis was performed based on the TCGA Head and Neck Squamous Cell Carcinoma (HNSCC) cohort in order to correlate patients’ survival with TIGIT and CD274 (encoding for PD-L1) gene expression levels. (3) Results: Database analysis revealed a beneficial outcome in OAS for tumor patients with high intraepithelial CD3-TIGIT-expression (n = 327). Hereby, OAS was 53.9 months vs. 30.1 months for patients with lower TIGIT gene expression levels (p = 0.033). In our retrospective OSCC-TMA cohort, elevated TIGIT levels on CD3+ cells correlated significantly with improved OAS (p = 0.025) as well as distant RFS (p = 0.026). (4) Conclusions: This study introduces TIGIT as a novel prognostic factor in OSCC, indicating the improved outcome of OSCC patients relative to their increased TIGIT expression. TIGIT might provide therapeutic implications for future immunotherapy in advanced-stage OSCC patients.

(1) Background: The radial forearm flap (RFF) has evolved as the flap of choice for intraoral mucosal reconstructions, providing thin and pliable skin with a safe blood supply. Perforator flaps such as the anterolateral thigh (ALT) flap are increasingly being discussed for the same applications. (2) Methods: Patient history, treatment details, and outcome of 12 patents with moderate to extended defects of the lip and/or nose area that were reconstructed by a folded radial forearm flap were retrospectively evaluated for oncologic and functional outcomes. (3) Results: The mean oncologic and functional follow-up were 21.1 (min. 3.8; max. 83.3) and 31.2 (min. 6; max. 96) months, respectively. All flaps survived without revision. In eight cases, major lip defects were reconstructed by an RFF; in six patients, the palmaris longus tendon was included for lip suspension. The functional results in terms of eating, drinking, and mouth opening were good in five cases, while three patients were graded as fair due to moderate drooling. In seven cases, the major parts of the nose were reconstructed with two good and five fair (nostril constriction in three cases) functional results. (4) Conclusions: The folded RFF remains a unique free flap option for complex three-dimensional lip and nose reconstructions in terms of flexibility, versatility, and robustness.