Given myeloid cells’ importance in driving antitumor activity, the decrease of DCs post-ICB therapy, and the association of TLSs with response to ICB, we set out to determine the effect of TLR8 agonist (motolimod), in combination with anti-PD-1 blockade (nivolumab) on the tumor ecosystem in HNSCC patients. The gene discussed is TLR8; the disease is head and neck squamous cell carcinoma.