Background: Intra-tumoral CD8 + T-cell infiltration in squamous cell carcinoma of the head and neck (HNSCC) has previously been linked to the efficacy of cisplatin-based chemoradiation (CDDP-CRTX) and immune checkpoint inhibitor (ICI) monotherapy.Further detailed characterization of the tumor immune-micromilieu and its influence on outcome may guide the development of CRTX-ICI combinations.Methods: Comprehensive immune transcriptome analysis was applied to a training set of tumor specimens from oropharyngeal squamous cell carcinoma (OPSCC) patients treated with Circle Pendant With Birthstone Beads Necklace CDDP-CRTX in the ARO-0401 phase III study (n = 33).A composite immune signature risk score (ISRS) for survival prediction was developed, and subsequently validated in two independent OPSCC cohorts treated with either CDDP-CRTX (n = 36) or mitomycin-based CRTX (MMC-CRTX, n = 31).Further validation of the ISRS was performed in the OPSCC subset (n = 79) of the TCGA HNSCC cohort.
Potential interference between immune signatures and HPV status was evaluated in multivariate Cox regression models.Results: Significant differences according to the 3-y OS status NUTRI FLEX in the abundance of tumor-infiltrating T- and B-cells, and the expression levels of 51 immune-related genes were observed.A risk score based on 13 differentially expressed genes involved in cytokine signaling, T-cell effector functions and the TNFR pathway was established as robust predictive factor of OS.Its predictive power was superior to the 6-gene interferon-gamma signature of ICI efficacy and independent of the HPV status.Conclusions: This study further elucidates the complex interaction of the tumor immune microenvironment with the efficacy of CDDP-CRTX in OPSCC.
The results suggest immune markers for selection of patients treated with CRTX-ICI combinations.