Analysis of tumor-infiltrating CD103 resident memory T-cell content in recurrent laryngeal squamous cell carcinoma

Background: Recurrent laryngeal squamous cell carcinomas (LSCCs) are associated with poor outcomes, without reliable biomarkers to identify patients who may benefit from adjuvant therapies. Given the emergence of tumor-infiltrating lymphocytes (TIL) as a biomarker in head and neck squamous cell carcinoma, we generated predictive models to understand the utility of CD4 ⁺ , CD8 ⁺ and/or CD103 ⁺ TIL status in patients with advanced LSCC. Methods: Tissue microarrays were constructed from salvage laryngectomy specimens of 183 patients with recurrent/persistent LSCC and independently stained for CD4 ⁺ , CD8 ⁺ , and CD103 ⁺ TIL content. Cox proportional hazards regression analysis was employed to assess combinations of CD4 ⁺ , CD8 ⁺ , and CD103 ⁺ TIL levels for prediction of overall survival (OS), disease-specific survival (DSS), and disease-free survival (DFS) in patients with recurrent/persistent LSCC. Results: High tumor CD103 ⁺ TIL content was associated with significantly improved OS, DSS, and DFS and was a stronger predictor of survival in recurrent/persistent LSCC than either high CD8 ⁺ or CD4 ⁺ TIL content. On multivariate analysis, an “immune-rich” phenotype, in which tumors were enriched for both CD103 ⁺ and CD4 ⁺ TILs, conferred a survival benefit (OS hazard ratio: 0.28, p = 0.0014; DSS hazard ratio: 0.09, p = 0.0015; DFS hazard ratio: 0.18, p = 0.0018) in recurrent/persistent LSCC. Conclusions: An immune profile driven by CD103 ⁺ TIL content, alone and in combination with CD4 ⁺ TIL content, is a prognostic biomarker of survival in patients with recurrent/persistent LSCC. Predictive models described herein may thus prove valuable in prognostic stratification and lead to personalized treatment paradigms for this patient population.