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ABSTRACT: 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.
SUBMITTER: Mann JE
PROVIDER: S-EPMC6375747 | biostudies-literature | 2019 Feb
REPOSITORIES: biostudies-literature
Mann Jacqueline E JE Smith Joshua D JD Birkeland Andrew C AC Bellile Emily E Swiecicki Paul P Mierzwa Michelle M Chinn Steven B SB Shuman Andrew G AG Malloy Kelly M KM Casper Keith A KA McLean Scott A SA Moyer Jeffery S JS Wolf Gregory T GT Bradford Carol R CR Prince Mark E ME Carey Thomas E TE McHugh Jonathan B JB Spector Matthew E ME Brenner J Chad JC
Cancer immunology, immunotherapy : CII 20181025 2
<h4>Background</h4>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<sup>+</sup>, CD8<sup>+</sup> and/or CD103<sup>+</sup> TIL status in patients with advanced LSCC.<h4>Methods</h4>Tissue mic ...[more]