Stromal tumor-associated eosinophils predict therapeutic resistance and survival in locally advanced tongue squamous cell carcinoma after neoadjuvant therapy

Background: Neoadjuvant therapy provides substantial clinical benefits for patients with locally advanced tongue squamous cell carcinoma (TSCC). It improves the rate of complete tumor resection, decreases recurrence risk, and extends survival. However, accurate post-therapy risk stratification depends on the identification of reliable prognostic biomarkers. Objectives: This retrospective study assessed several immune microenvironment biomarkers—tumor-associated tissue eosinophils (TATEs), neutrophils (TANs), lymphocytes (TILs), and tertiary lymphoid structures (TLSs)—in 108 patients with stage III or IV TSCC who received neoadjuvant chemotherapy ( n = 44) or immunochemotherapy ( n = 64) between 2013 and 2022. Design: Retrospective cohort study. Methods: Post-treatment hematoxylin and eosin (H&E)-stained specimens were evaluated to quantify biomarker infiltration. Associations between biomarker levels, pathological response, and survival outcomes were analyzed. Results: A low stromal TATE (S-TATE) density (⩽20/mm²) was significantly correlated with higher rates of pathological complete response (pCR) ( p < 0.001). In contrast, elevated S-TATE levels were associated with lymph node metastasis ( p = 0.011) and vascular or neural invasion ( p = 0.004). Multivariate analysis identified S-TATE > 20/mm² as an independent predictor of reduced overall survival (HR = 3.52, 95% CI: 1.01–12.32; p = 0.049) and shorter progression-free survival. Conclusion: S-TATE serves as an independent prognostic indicator in patients with locally advanced TSCC receiving neoadjuvant therapy. Quantifying S-TATE in post-treatment specimens may help tailor adjuvant therapy intensity and refine surveillance strategies. Patients with elevated S-TATE levels should receive closer follow-up.