Genetic and epigenetic features of head and neck tumors with variable molecular immune signatures

BackgroundMalignant progression exhibits a tightly orchestrated balance between immune effector response and tolerance. However, underlying molecular principles that drive the establishment and maintenance of the tumor immune phenotype remain to be elucidated.

Experimental designA molecular classifier based on immune cell subsets related to CD274 and IFNG expression was trained and revealed groups with or without a cytotoxic immune phenotype. Integrative analysis of multi-omics data was conducted for differences in genetic and epigenetic landscapes, and to identify their impact on differentially expressed genes (DEG) among immune phenotypes. A prognostic gene signature was established by a LASSO-Cox regression model.

ResultsMutational landscape analyses elucidated characteristic differences in somatic mutations and copy-number alterations among tumors with a variable immunophenotype. An integrative multi-omics approach identified the epidermal growth factor receptor (EGFR) and the prostaglandin-endoperoxide synthase 2 (PTGS2) as key nodes in a network related to the immunophenotype. In addition, several immune-related genes are affected by EGFR inhibition in tumor cell lines. A prognostic gene signature was established by a LASSO-Cox regression model based on DEGs between cancer patients with a non-progressive or progressive disease under ICI treatment.

Conclusions: Our data highlight a complex interplay between genetic and epigenetic events in the establishment of the tumor immunophenotype, and we provide compelling experimental evidence that a HNSCC patient at higher risk for ICI treatment failure might benefit from a combination with EGFR and/or PTGS2 inhibition.

Poster-PDF A-1531.pdf

„Gesetzten Vortrag“ aus der Heidelberger Univ. HNO-Klinik

Publikationsverlauf

Artikel online veröffentlicht:
13. Mai 2021