This suggests that SUV420H1 depletion in HPV-negative HNSCC tumors may synergize with anti-PD-1 immune checkpoint blockade by (i) inducing the re-expression of IFN-response genes, (ii) increasing the intratumoral influx of macrophages and decreasing that of gMDSCs towards a more immunostimulatory TIME through transcriptional regulation of myeloid-attracting chemokines/cytokine genes IL1A, IL1B, LPAR1, CXCL1, CXCL8, IL15 and IL6, and (iii) by promoting the anti-tumorigenic function of macrophages. Here, IL15 is linked to head and neck squamous cell carcinoma.