Dendritic cell effector mechanisms and tumor immune microenvironment infiltration define TLR8 modulation and PD-1 blockade

The potent immunostimulatory effects of toll-like receptor 8 (TLR8) agonism in combination with PD-1 blockade has resulted in a variety of preclinical investigations, yet the mechanism of action in humans remains unknown. We used scRNAsequencing and multi-spectral spatial imaging to elucidate the tumor immune microenvironment and correlates to response to a a unique open-label phase 1b pre-operative window of opportunity clinical trial (NCT03906526) in head and neck squamous cell carcinoma (HNSCC) Overall design: scRNAseq was performed on three head and neck squamous cell carcinoma patient samples treated with a TLR8 agonist (Motolimod) and anti-PD1 therapy (Nivolumab) pre and post therapy.