Interference of tumor mutational burden with outcome of patients with head and neck cancer treated with definitive chemoradiation: A multicenter retrospective study of the German Cancer Consortium Radiation Oncology Group (DKTK-ROG). Interference of tumor mutational burden with outcome of patients with head and neck cancer treated with definitive chemoradiation: A multicenter retrospective study of the German Cancer Consortium Radiation Oncology Group (DKTK-ROG)

It has been postulated that a high number of mutations resulting in the expression of neoantigens promotes T-cell-mediated inflammation and, as a consequence leads to the activation of immune checkpoints Hence, we determined if high tumor mutational burden (TMB) was associated with a distinct immune expression signature. For this analysis, 37 cases with tumor material for nanoString mRNA expression analysis were available. Overall, only minor differences in the expression levels of the immune-related genes were observed. Specific features of immune checkpoint activation such as high CD8+ T-cell scores and the IFNG signature were downregulated per trend in high compared to low TMB cases. In contrast, genes involved in neutrophil functions were found to be overexpressed in the high TMB group. Overall design: Immune gene expression profiles were established in a cohort of patients with histologically proven locally advanced squamous cell carcinoma of the oral cavity (N=5), oropharynx (N=18) or hypopharynx (N=14) from a retrospective multicenter DKTK-ROG biomarker study. Treatment protocol was according to standard concurrent chemoradioation (cCRTX) including cisplatin/5-fluorouracil (N=33) or mitomycin-C/5-fluorouracil (N=4). RNA was isolated from FFPE tumor specimens and analysed by using the nCounter PanCancer Immune Profiling Panel and the nCounter Digital Analyzer. Differences in basal mRNA levels of the included immune-related genes and the abundance of immune-cell subsets according to the TMB status were established.