Cellular senescence as prognostic biomarker and herapeutic target in HNSCC

Background The tumor environment controls nutrient and oxygen supply as well as immune surveillance of malignant tumors, thus representing both biological prerequisite and therapeutic vulnerability in cancer. Recently, cellular senescence emerged as a fundamental characteristic of solid malignancies. We therefore hypothesize that senescence in the tumor environment serves as a promising prognostic and therapeutic target in head and neck squamous cell carcinoma (HNSCC).

Methods Human single-cell RNA sequencing datasets of solid malignancies were employed to generate a transcriptomic signature based on senescence in the tumor environment. Utilizing this gene signature, machine learning algorithms were applied to construct survival prognostication models. Towards a therapeutic perspective, a mouse model of HNSCC (cell line SCC VII) was used to evaluate effects of senolytic and -morphic drugs on tumor growth.

Results Here, we developed a senescence-related transcriptomic signature, which positively correlates with impaired survival in HNSCC. Combining clinical patient data with a risk score relying on this gene signature further enhanced the accuracy of this survival prognostication model. In accordance with these findings, administration of senolytic or -morphic drugs significantly reduced tumor progression in experimental HNSCC.

Conclusions Hence, senescence in the tumor environment is related to poor survival in HNSCC. Senolytic or -morphic drugs might consequently be beneficial in the treatment of HNSCC.

This study is supported by collaborative research centre 914 of Deutsche Forschungsgemeinschaft.

Publication History

Article published online:
12 May 2023