Background: Immune cell heterogenicity is known to determine the therapeutic response to cancer progression. Neoadjuvant chemoimmunotherapy (NACI) has shown clinical benefits in some patients with advanced head and neck squamous cell carcinoma (HNSCC), but the underlying mechanism behind this clinical response is unknown. The efficacy of NACI needs to be potentiated by identifying accurate biomarkers to predict clinical responses. Here, we attempted to identify molecules predicting NACI response in advanced HNSCC. Methods: We performed combined single‐cell RNA sequencing (scRNA‐seq) and multiplex immunofluorescence (mIHC) staining with tumor samples derived from NACI‐treated HNSCC patients to identify a new tumor‐infiltrating cell (TIL) subtype, CD103 ⁺ CD8 ⁺ TILs, associated with clinical response, while both in vitro and in vivo assays were carried out to determine its antitumor efficiency. The regulatory mechanism of the CD103 ⁺ CD8 ⁺ TILs population was examined by performing cell‐cell interaction analysis of the scRNA‐seq data and spatial analysis of the mIHC images. Results: We established intratumoral CD103 ⁺ CD8 ⁺ TILs density as a determinant of NACI efficacy in cancers. Our scRNA‐seq results indicated that the population of CD103 ⁺ CD8 ⁺ TILs was dramatically increased in the responders of NACI‐treated HNSCC patients, while mIHC analysis confirmed the correlation between intratumoral CD103 ⁺ CD8 ⁺ TILs density and NACI efficacy in HNSCC patients. Further receiver operating characteristic curve analysis defined this TIL subset as a potent marker to predict patient response to NACI. Functional assays showed that CD103 ⁺ CD8 ⁺ TILs were tumor‐reactive T cells, while programmed cell death protein‐1 (PD‐1) blockade enhanced CD103 ⁺ CD8 ⁺ TILs cytotoxicity against tumor growth in vivo. Mechanistically, targeting the triggering receptor expressed on myeloid cells 2‐positive (TREM2 ⁺ ) macrophages might enhance the population of CD103 ⁺ CD8 ⁺ TILs and facilitate antitumor immunity during NACI treatment. Conclusions: Our study highlights the impact of intratumoral CD103 ⁺ CD8 ⁺ TILs density on NACI efficacy in different cancers, while the efforts to elevate its population warrant further clinical investigation.

Background: Surgery and postoperative adjuvant therapy is the standard treatment for locally advanced resectable oral squamous cell carcinoma (OSCC), while neoadjuvant chemoimmunotherapy (NACI) is believed to lead to better outcomes. This study aims to investigate the effectiveness of NACI regimens in treating locally advanced resectable OSCC. Materials and methods: Patients diagnosed with locally advanced resectable OSCC who received NACI and non-NACI were reviewed between December 2020 and June 2022 in our single center. The pathologic response was evaluated to the efficacy of NACI treatment. Adverse events apparently related to NACI treatment were graded by Common Terminology Criteria for Adverse Events, version 5.0. The disease-free survival (DFS) and overall survival (OS) rate were assessed. Results: Our analysis involved 104 patients who received NACI. Notably, the pathological complete response rate was 47.1%, and the major pathological response (MPR) rate was 65.4%. The top three grade 1–2 treatment-related adverse events (TRAEs) were alopecia (104; 100%), anemia (81; 77.9%), and pruritus (62; 59.6%). Importantly, patients achieving MPR exhibited higher programmed cell death-ligand 1 (PD-L1) combined positive scores (CPS). The diagnostic value of CPS as a biomarker for NACI efficacy was enhanced when combined with total cholesterol level. The 3-year estimated DFS rates were 89.0% in the NACI cohort compared to 60.8% in the non-NACI cohort, while the 3-year estimated OS rates were 91.3 versus 64.0%, respectively. Conclusions: The NACI treatment showed safe and encouragingly efficacious for locally advanced resectable OSCC patients. The high response rates and favorable prognosis suggest this approach as a potential treatment option. Prospective randomized controlled trials are needed to further validate these findings.

The aim of this study was to evaluate the efficacy of the retromandibular approach (RMA) to produce three-dimensional (3-D) reduction of the unilateral subcondylar fracture and Temporomandibular Joint (TMJ) functional implication. Methods: A prospective cohort study was designed. Twenty-nine patients with unilateral subcondylar fracture underwent consecutively Open Reduction, and Internal Fixation. The cohorts were divided into two groups; RMA group (n = 16, 55.17%) and submandibular approach SMA group (n = 13, 44.82%). The primary outcome was the anatomical 3-D reduction of the condyle. The secondary outcome was to compare the condyle position and inclination finding with TMJ outcomes. Helkimo Index score was used to evaluate the TMJ outcome at six months postoperatively. Result: There was a significant difference between the mediolateral condylar inclination, condylar medial and vertical positions when RMA compared with SMA groups (P < 0.05). The medial joint space was correlated with the medial condylar position in both groups (P < 0.05). The Helkimo Ai and Di was associated with mediolateral condylar inclination in SMG; however, Helkimo Ai was found to be correlated with the RMA group. Conclusion: The current study demonstrates that the RMA could re-establish the anatomical position of the unilateral subcondylar fracture in patients undergoing ORIF. The clinical outcome of the TMJ with RMA was better than SMA.