Immune checkpoint inhibitors (ICIs), including anti-programmed cell death 1 ligand 1 (PD-L1) antibodies, are significantly changing treatment strategies for human malignant diseases, including oral cancer. Cancer cells usually escape from the immune system and acquire proliferative capacity and invasive/metastatic potential. We have focused on the two immune checkpoints, PD-1/PD-L1 and CD47/SIRPα, in the tumor microenvironment of oral squamous cell carcinoma (OSCC), performed a retrospective analysis of the expression of seven immune-related factors (PD-L1, PD-1, CD4, CD8, CD47, CD56 and CD11c), and examined their correlation with clinicopathological status. As a result, there were no significant findings relating to seven immune-related factors and several clinicopathological statuses. However, the immune checkpoint-related factors (PD-1, PD-L1, CD47) were highly expressed in non-keratinized epithelium-originated tumors when compared to those in keratinized epithelium-originated tumors. It is of interest that immunoediting via immune checkpoint-related factors was facilitated in non-keratinized sites. Several researchers reported that the keratinization of oral mucosal epithelia affected the immune response, but our present finding is the first study to show a difference in tumor immunity in the originating epithelium of OSCC, keratinized or non-keratinized. Tumor immunity, an immune escape status of OSCC, might be different in the originating epithelium, keratinized or non-keratinized.

Immune checkpoint inhibitors (ICIs), including anti-programmed cell death 1 ligand 1 (PD-L1) antibodies, are significantly changing treatment strategies for human malignant diseases including oral cancer. Cancer cells usually escape from immune system and acquire proliferative capacity and invasive/metastatic potential. We have focused on the two immune checkpoints, PD-1/PD-L1 and CD47/SIRPα in the tumor microenvironment of oral squamous cell carcinoma (OSCC), and performed a retrospective analysis of the expression of seven immune-related factors (PD-L1, PD-1, CD4, CD8, CD47, CD56 and CD11c), and examined their correlation with clinicopathological status. As a result, there were no significant findings relating seven immune-related factors and several clinicopathological statuses. However, the immune-checkpoint related factors (PD-1, PD-L1, CD47) were highly expressed in non-keratinized epithelium-originated tumors when compared to those in keratinized epithelium-originated tumors. It is of interest that immunoediting via immune checkpoint-related factors was facilitated in non-keratinized sites. Several researchers reported that keratinization of oral mucosal epithelia affected the immune response, but our present finding is the first study to show a difference of the tumor immunity in the originating-epithelium of OSCC, keratinized or non-keratinized. Tumor immunity, an immune escape status of OSCC might be different in the originating-epithelium, keratinized or non-keratinized.

In this study, we examined the current situation of the dental implant treatments in patients with extensive jaw defects after treatment for various oral and maxillofacial diseases. Additionally, we extracted factors related to the loss of dental implants and assessed the recovery of the masticatory function of the patients. Forty-three patients with extensive jaw defects who underwent dental implant treatments covered by Jap-anese public health insurance at Dokkyo Medical University Hospital were included in this study. The primary diseases of the patients were malignant tumor (n=24), benign tumor (n=12), cleft lip and palate (n=3), trauma (n=2), and osteonecrosis (n=2). One hundred fourteen dental implants were placed in 43 patients, and 9 dental implants were lost during early period of the treatment. The masticatory function in 7 patients with a removable denture on dental implants increased significantly from before to af-ter denture placement (p=0.008). The masticatory function in 3 patients with fixed prosthesis was similar to that in 3 healthy individuals with natural dentition. In uni-variate analysis, loss of dental implants was higher in patients with maxillary dental implants (p=0.025), maxillary cantilever denture retained with implants on existing maxillary bone (p=0.032), and patients who received radiotherapy (p=0.034). In multi-variate analysis, p value of these 3 risk factors did not reach significant level. Despite the complicated surgical conditions and limited option of prosthesis in the patients with extensive jaw defects, good outcomes were achieved and the dental implant treatments improved their masticatory function.

Background: The majority of cleft palate patients have been reported to suffer from otitis media with effusion (OME). The improvement of velopharyngeal function (VPF) after palatoplasty might be evidence for the improvement of the function of the Eustachian tube. The improvement of the function of Eustachian tube by palatoplasty has been reported to be effective for the treatment of OME simultaneously with the insertion of a ventilation tube into the tympanic membrane. There are only a few reports that clearly show the association between improvement of VPF and improvement of OME after palatoplasty. In this study, we discussed whether the improvement of VPF after palatoplasty in cleft palate patients with OME improved OME. Methods: Twenty-six patients with cleft palate were included in the study. We retrospectively extracted the information of cleft type, gender, surgical technique, and presence of OME risk factors from electronic medical records. We also investigated the recurrence of OME and the improvement level of VPF at 36 months postoperatively. OME was assessed based on the otolaryngologist’s findings in electronic medical records, with a good prognosis group with no symptom of OME, or a recurrence group with prolonged or recurrent OME. Results: At 36 months after palatoplasty, 19 of 23 patients (82.6%) were in the OME good prognosis group and four (17.4%) were in the OME recurrence group. The rate of patients with recurrent OME did not differ significantly by the degree of improvement of VPF. This study indicated that clear association between other risk factors for OME and OME recurrence could not be shown. Conclusion: We observed that most patients with cleft palate who underwent palatoplasty showed a good prognosis for OME at 36 months after surgery. However, further studies are needed to investigate the impact of different surgical techniques on the improvement of OME and the degree to which VPF improves, as well as the effect of each OME risk factor.

Oral lichen planus (OLP) is a chronic inflammatory mucosal disease, and an apparent cause has not been identified. OLP is refractory to treatment, and malignant transformation has been reported. Therefore, discovering effective drugs with few adverse effects over long-term administration is crucial. In this study, we established an in vitro OLP model to investigate the effects of Cepharanthin®, an alkaloid mixture derived from Stephania cephalantha Hayata. Four alkaloids from Cepharanthin® suppressed the expression of cytokine genes at various degrees in activated T cells. However, the effect of Cepharanthin® was limited. On the other hand, Cepharanthin® and four alkaloids suppressed the expression of various cytokine genes in human oral epithelial cells when stimulated with IL-β. In the OLP model, activated T cells increased the inflammatory gene expression in the epithelial cells, while Cepharanthin® suppressed their gene expression. Anti-inflammatory effect of Cepharanthin® was observed by protein dot blot. The effects of Cepharanthin®️ might be expressed through two aspects: its effect of mildly suppressing the activation of T lymphocytes and strongly suppressing the response of epithelial cells to inflammatory stimuli. The in vitro model established in this study could be a tool for elucidating the mechanisms of OLP pathogenesis and disease persistence.