Given the standard of care role of anti-PD-1 immunotherapy in the treatment of HPV-negative HNSCC (3) and the fact that IFN-response signatures were enriched in human tumors with SUV420H1 mRNA overexpression (Fig. 1C), we opted to evaluate the effect of Suv420h1 in the tumor immune microenvironment (TIME) of mouse HPV-negative HNSCC tumors in vivo. Here, KMT5B is linked to head and neck squamous cell carcinoma.