Dehydroepiandrosterone attenuated the immune escape of oral squamous cell carcinoma through NF-κB p65/miR-15b-5p/B7-H4 axis.

OBJECTIVES: We aimed to explore the effects and mechanisms of action of dehydroepiandrosterone (DHEA) on immune evasion of oral squamous cell carcinoma (OSCC) to provide evidence for enhancing the effect of immunotherapy. MATERIALS AND METHODS: A xenograft mouse model and immunohistochemistry were used to reveal the patterns of tumor-infiltrating lymphocytes (TILs). The CAL27 and SCC VII cell lines were used for the in vitro study. Western blotting, qPCR, immunofluorescence, and flow cytometry were used to evaluate the expression of B7-H4. Recombinant mouse B7-H4 protein (rmB7-H4) and PG490, an inhibitor of NF-κB p65 were used for the "rescue study." Gain- and loss-of-function, luciferase reporter, and chromatin immunoprecipitation assays were performed to verify this mechanism. RESULTS: DHEA inhibited tumor growth in an OSCC xenograft mouse model, increased CD8 + cells, and decreased FOXP3 + cells in TILs. DHEA reduced the expression of B7-H4 in CAL27 and SCC VII cells RmB7-H4 reverses the effect of DHEA on tumor growth and TIL patterns. DHEA increased the expression of miR-15b-5p and activated its transcriptional factor NF-κB p65. Further experiments demonstrated that miR-15b-5p inhibited B7-H4 expression by binding to its 3'-UTR regions, and NF-κB p65 activated miR-15b transcription. PG490 reversed the effects of DHEA on tumor growth, antitumor immunity in the OSCC xenograft model, and the expression/phosphorylation of NF-κB p65, miR-15b-5p, and B7-H4. CONCLUSIONS: This study indicates that DHEA attenuates the immune escape of OSCC cells by inhibiting B7-H4 expression, providing new insights for cancer immunotherapy.

Digitally designed stent-assisted soft-tissue management after jaw reconstruction: a prospective cohort study.

OBJECTIVES: A digitally designed stent was invented to assist vestibuloplasty and free gingival graft (FGG) after jaw reconstruction. This study aimed to compare the effects of conventional soft-tissue management comprising vestibuloplasty combined with FGG and modified soft-tissue management using a digitally designed stent on the vestibular sulcus depth (VD), keratinised-tissue width (KTW) and peri-implant tissue health in patients undergoing jaw reconstruction. MATERIALS AND METHODS: This prospective cohort study enrolled patients who underwent jaw reconstruction using a fibular flap, iliac flap, or onlay bone graft followed by implant-supported rehabilitation at the Peking University School and Hospital of Stomatology between May 2019 and July 2022. Patients in the stent group received digitally designed stents following vestibuloplasty combined with FGG for peri-implant soft-tissue management. Patients in the control group underwent a conventional vestibuloplasty combined with FGG. VD and KTW were evaluated immediately after implant loading (T2) and 1 year after implant loading (T3), and the atrophy rates of VD and KTW were calculated. Peri-implant clinical parameters were evaluated at T3. Comparisons between the groups were performed using the Mann-Whitney U test. The effects of age, sex, primary disease, reconstruction type, reconstructed jaw and the number and location of implants on VD and KTW were evaluated using linear regression analysis. RESULTS: There were no significant differences in the atrophy rates of VD and KTW between the stent and control groups at T2 and T3 (both P ≥ 0.05). There were no significant differences in peri-implant clinical parameters between the stent and control groups at T3 (P ≥ 0.05). Reconstruction type, location of implants and primary disease influenced VD, and reconstruction type and age influenced KTW. CONCLUSIONS: There was no significant difference in the maintenance of VD and KTW after jaw reconstruction between soft-tissue management using a digitally designed stent and the conventional method. Further, digitally designed stents do not affect peri-implant tissue health. CLINICAL RELEVANCE: Digitally designed stents can simplify clinical procedures without adverse effects on peri-implant tissue health, but they do not promote keratinized mucosa augmentation and vestibuloplasty.

Accurate Reconstruction of Mandibular Defects With Vascularized Bone Flaps Through Utilization of Mandible Space-Retention Guides.

PURPOSE: Comprehensive evaluation of the effects of using computer-aided design and space retention guide technology to reconstruct mandibular defects using vascularized autogenous bone flaps. METHOD: This study included 8 patients who received autogenous bone flaps (2 cases of vascularized fibula flaps and 6 cases of vascularized iliac flaps) for mandibular defect reconstruction at Peking University School and Hospital of Stomatology, from July 2018 to May 2021. All patients received digital surgery planning, computer aided design/computer aided manufacture, surgical guide technique for the removal of diseased bone segments, as well as vascularized fibular flap/iliac flap reconstruction. Three-dimensional deviations were analyzed after the operation. RESULT: The mandibular defects of all 8 patients were successfully reconstructed using the vascularized fibular flap/iliac bone flap. There were no serious complications at either the donor site or recipient site during our follow-up. The average three-dimensional deviation of all 8 patients was 1.92 mm, based on comparisons of preoperative design and actual postoperative computed tomography. CONCLUSION: Utilizing computer aided design/computer aided manufacture, we designed a new mandibular space-retention guide, which can accurately translate the preoperative digital design plan to real-time surgery with satisfactory accuracy and efficacy.

Soft Tissue Management: A Critical Part of Implant Rehabilitation After Vascularized Free-Flap Reconstruction.

PURPOSE: Implant rehabilitation after jaw reconstruction is challenging, and postoperative peri-implantitis is common. Our aim was to present our management protocol for implant rehabilitation after vascularized free-flap reconstruction and report the outcomes of soft tissue management. METHODS: This retrospective cohort study included patients who received vascularized free-flap reconstruction, implant rehabilitation, apical reposition flaps (ARFs), and free gingival grafts (FGGs) at Peking University School and Hospital of Stomatology from January 1, 2009 to January 1, 2020. We assessed the association of age, gender, primary disease, flap choice, number and position of implants, timing of ARFs and FGGs, fixation stent use, and restoration type with the occurrence of peri-implantitis. Probing pocket depth, bleeding on probing, and marginal bone loss of the implants were measured as well. The data were analyzed by descriptive statistics, Kaplan-Meier statistics, and Cox regression analysis. RESULTS: In total, 19 patients with 65 implants were included. The implants were placed immediately or 7 to 44 months after reconstruction of the jaw with fibular (n = 17) or iliac flaps (n = 2). ARFs and FGGs were performed 0 to 11 months later. No implants were lost. The mean probing pocket depth, bleeding on probing, and marginal bone loss at 26.6 ± 16.8 months were 3.5 ± 0.9 mm, 70.4 ± 35.1%, and 0.6 ± 0.4 mm, respectively. The incidence of peri-implantitis was 32.3%, showing no significant associations with the gender, age, primary disease, flap choice, number and position of implants, timing of ARFs and FGGs, use of a fixation stent, and type of restoration based on the adjusted multivariate model (P > .05). CONCLUSIONS: Soft tissue management helps generate firmly attached keratinized mucosa around the implants, leads to a more precise impression, and reduces peri-implant bone loss. It should be considered as a critical part of implant rehabilitation after vascularized free-flap reconstruction.