Smyd3-mediated immuno-modulation in HPV-negative head and neck squamous cell carcinoma mouse models.

ABSTRACT: SET and MYND-domain containing protein 3 (SMYD3) mediates epigenetic repression of type I IFN response genes in human papillomavirus (HPV)-negative HNSCC cells, and Smyd3 depletion using anti-sense oligonucleotides (ASOs) increases the sensitivity of syngeneic mouse oral carcinoma (MOC1) models to anti-PD-1 therapy. In this study, we utilized single-cell RNA-seq of MOC1 tumors treated with Smyd3 ASOs and found enrichment of type I IFN response pathways in cancer cells, a shift of CD8⁺ T-cells toward an activated/memory phenotype, and a shift of neutrophils toward an anti-tumorigenic phenotype. Mechanisms of resistance to the Smyd3 ASO and anti-PD-1 combination were derived from cancer cells, macrophages, and CD8⁺ T-cells, including neutrophil enrichment through the up

SUBMITTER: Tsai DE 

PROVIDER: S-EPMC11416682 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature