By sorting receptor tyrosine kinases into endolysosomes, the endosomal sorting complexes required for transport (ESCRTs) are thought to attenuate oncogenic signaling in tumor cells. Paradoxically, ESCRT members are upregulated in tumors. Here, we show that disruption of hepatocyte growth factor-regulated tyrosine kinase substrate (HRS), a pivotal ESCRT component, inhibited tumor growth by promoting CD8⁺ T cell infiltration in melanoma and colon cancer mouse models. HRS ablation led to misfolded protein accumulation and triggered endoplasmic reticulum (ER) stress, resulting in the activation of the type I interferon pathway in an inositol-requiring enzyme-1α (IRE1α)/X-box binding protein 1 (XBP1)-dependent manner. HRS was upregulated in tumor cells with high tumor mutational burden (TMB). HRS expression associates with the response to PD-L1/PD-1 blockade therapy in melanoma patients with high TMB tumors. HRS ablation sensitized anti-PD-1 treatment in mouse melanoma models. Our study shows a mechanism by which tumor cells with high TMB evade immune surveillance and suggests HRS as a promising target to improve immunotherapy.

Maxillary deficiency, a common transversal dentofacial deformity, affects aesthetics and function. Timely intervention during adolescence is crucial, as the growth potential of the maxilla provides an opportunity to optimize treatment outcomes. This review explores various approaches for adolescent maxillary expansion, including orthopedic and surgical methods. Orthopedic appliances effectively address transverse deficiencies without surgery and are particularly beneficial in managing conditions in children and early adolescents. In mid- to late-stage adolescents, bone-borne devices with mini-surgery offer better skeletal expansion outcomes. However, in cases of severe deficiencies, or where skeletal resistance limits non-surgical methods, surgical interventions become essential. Procedures like surgically assisted maxillary expansion and orthognathic surgery offer superior skeletal corrections. These techniques are particularly valuable for late adolescents with complex conditions. This review comprehensively summarizes the applications, outcomes, and limitations of these treatment options, highlighting the importance of selecting individualized, growth stage-appropriate interventions.

Objectives: To present the use of dynamic navigation system in the repair of alveolar cleft. Patients and Participants: A total of three non-syndromic patients with unilateral alveolar cleft were involved in this study. Real-time computer-aided navigation were used to achieve restoration and reconstruction with standardized surgical technique. Methods: With the individual virtual 3-dimensional (3-D) modeling based on computed tomography (CT) data, preoperative planning and surgical simulation were carried out with the navigation system. During preoperative virtual planning, the defect volume or the quantity of graft is directly assessed at the surgical region. With the use of this system, the gingival periosteum flap incision can be tracked in real-time, and the bone graft can be navigated under the guidance of the 3-D views until it matches the preoperatively planned position. Results: Three patients with alveolar cleft were successfully performed under navigation guidance. Through the model alignment procedure, accurate matches between the actual intraoperative position and the CT images were achieved within the systematic error of 0.3 mm. The grafted bone was implanted according to the preoperative plan with the aid of instrument- and probe-based navigation. All the patients were healed well without serious complications. Conclusions: These findings suggest that image-guided surgical navigation, including preoperative planning, surgical simulation, postoperative assessment, and computer-assisted navigation was feasible and yielded good clinical outcomes. Clinical relevance: This dynamic navigation could be proved to be a valuable option for this complicated surgical procedure in the management of alveolar cleft repair.