Comprehensive Characterization of the Tumor Immune Micromilieu and its Interference with Outcome After Concurrent Chemoradiation in Patients with Locally Advanced Oropharyngeal Carcinomas

Intratumoral CD8+ T-cell infiltration in squamous cell carcinoma of the head and neck (HNSCC) has previously been linked to the efficacy of chemoradiation (CRTX) and immune checkpoint inhibitor (ICI) monotherapy. Further detailed characterization of the tumor immune-micromilieu and its influence on outcome may suggest rational CRTX-ICI combinations. In this study, the complex interaction of the tumor immune microenvironment with the efficacy of CRTX in HNSCC was analyzed. Comprehensive immune transcriptome analysis of FFPE tumor samples from patients with oropharyngeal carcinoma was used for establishing differences in tumor immune profiles according to the overall survival status. Furthermore, a composite immune signature risk score for survival prediction was developed. Immune profiles were established in a training set of FFPE tumor specimens from oropharyngeal squamous cell carcinoma (OPSCC) patients treated with cisplatin-based CTRX in the ARO-0401 phase III study (n=33) using the nCounter PanCancer Immune Profiling Panel and the nCounter Digital Analyzer. Differences in basal mRNA levels of 730 immune-related genes and the abundance of immune-cell subsets according to the overall survival (OS) status were established. A composite immune signature risk score for survival prediction was developed in the training set and validated in two independent OPSCC CRTX cohorts (validation 1, n=31; validation 2, n=36) and the OPSCC subset of the TCGA HNSCC cohort (validation 3, n=79), data of which is publicly available from the TCGA project.