Single‐Cell Profiling Reveals Stromal‐Immune Remodeling in <scp>HNSCC</scp> After <scp>TPF</scp> ‐Based Neoadjuvant Chemotherapy

ABSTRACT Objectives Neoadjuvant chemotherapy is widely used in patients with locally advanced head and neck squamous cell carcinoma. While tumor tissues often show significant regression after treatment, the changes that occur in the tumor microenvironment postregression remain largely unknown. Materials and Methods We performed single‐cell RNA sequencing on tumor and paracarcinoma tissue samples from three tongue cancer patients who underwent direct surgery, as well as on tumor, paracarcinoma tissue, and tumor stroma from three tongue cancer patients who received TPF‐based neoadjuvant chemotherapy. Results Single‐cell RNA sequencing identified distinct cellular features across tissue regions. Regression areas showed relatively greater representation of CFD + fibroblasts, whereas residual tumor cores retained POSTN + fibroblasts. Patient‐averaged T‐cell functional scores did not differ significantly among regions. Conclusions Regression areas and residual tumor cores in tongue squamous cell carcinoma after TPF‐based neoadjuvant chemotherapy exhibited distinct cellular and transcriptional features. These exploratory findings suggest regional heterogeneity of the post‐treatment tumor microenvironment and require validation in larger, spatially resolved cohorts.