UC Davis

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.