NOTCH1 and the tumor microenvironment of the head and neck squamous cell carcinoma

Introduction In search of a valid prognostic marker for HNSCC, NOTCH1 came up as a commonly mutated gene in whole-exome sequencing of HNSCC specimen. The aim of this project is to get further insight into the underlying functional mechanisms of NOTCH1 in HNSCC, potentially establishing NOTCH1 as a prognostic marker or therapeutic target for HNSCC. Additionally, interactions of NOTCH1 with the immune system were investigated.

Methods NOTCH1 was knocked down via RNA interference in HPV-positive and HPV-negative cell lines and the impact was evaluated in various functional assays. Additionally, cells were treated with DAPT or DLL4, an inhibitor or stimulator of NOTCH1-receptor, respectively. Afterwards the expression of NOTCH1, CD3 and CD8 was examined by immunohistochemistry in 70 oropharyngeal squamous cell cancer FFPE tissue samples.

Results Knockdown of NOTCH1 resulted in a decrease in migration and proliferation, whereas the NOTCH1 ligand DLL4 could increase proliferation of HNSCC cells. These findings were independent from the HPV status. In our IHC cohort, NICD was upregulated in OPSCC and a high expression was associated with advanced T stage and poor overall survival. The Immunoscore showed a better survival in patients with high infiltration of T lymphocytes. There was not association with NICD expression.

Conclusions NOTCH1 is involved in migration and proliferation of HNSCC cell lines. These findings are consistent with in vivo correlation of the increased NICD expression and advanced T stage in OPSCC. Strong infiltration of T lymphocytes was a prognostic factor.

Poster-PDF A-1106.pdf

Publication History

Article published online:
13 May 2021