ArticleFrontiers in immunology2026
Integrating clinicopathologic factors with whole-exome sequencing and peripheral immune repertoire sequencing to optimize decision-making in neoadjuvant chemoimmunotherapy for HNSCC.
Article in Frontiers in immunology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background: Neoadjuvant chemoimmunotherapy (NACIT) improves survival in patients with locally advanced head and neck squamous cell carcinoma (HNSCC), but optimal decisions remain challenging. Clinicopathological factors combined with whole-exome sequencing (WES) and peripheral immune repertoire sequencing (IRS) are promising for identifying prognostic factors to provide insights for clinical decisions and underlying mechanisms. Methods: Patients with locally advanced HNSCC treated with NACIT across 3 studies were included. Clinicopathological factors labeled with different time points, integrated with WES mutation features, peripheral IRS indices and clonotypes, were analyzed. The endpoints were overall survival (OS), event-free survival (EFS), and major pathological response (MPR). Multivariate logistic regression and Cox proportional hazards models were used to identify independent prognostic factors. Correlation analyses were used to explore the associations between sequencing indices and clinicopathological characteristics. Results: A total of 101 patients were included, with a median follow-up of 38 months, (from 2 to 55 months). Pathology revealed 50 (49.5%) patients with an MPR and 32 (31.7%) with a pathological complete response (pCR). The 3-year OS and EFS rates were 69.4% and 60.1%, respectively. Clinically, performance status (PS) was found to be associated with not only survival but also response. A positive surgical margin caused by extranodal extension significantly affects survival. Biologically, the IRS model based on specific T-cell and B-cell clonotypes demonstrated potential utility in predicting prognosis. High immune repertoire diversity and clonality were significantly correlated with better PS and primary tumor. The WES model showed limited prognostic utility while patients with Conclusion: Clinically, the PS was related to response and survival. ENE associated positive surgical margins remain a threat to survival. Biologically, the IRS model shows preliminary potential for patient stratification, warranting further investigation. Correlations of increased immune diversity with better physical status and primary tumor support earlier NACIT and are worthy of further exploration.
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