Nanosized Shikonin Disrupts Tumor-Cell Mismatch Repair and Synergizes with Manganese to Sensitize Squamous Carcinoma to Immunotherapy.

ABSTRACT: Head and neck squamous cell carcinoma (HNSCC) frequently develops resistance to immune checkpoint blockade (ICB) therapy, resulting from an immune-excluded microenvironment. Immunogenic cell death (ICD) can increase tumor immunogenicity and further augment immune-cell infiltration by releasing immunogenic molecules. Hence, inducing ICD within tumors might be a promising strategy to restore antitumor immunity and sensitize HNSCC to ICB. Herein, we developed shikonin (SHK)-loaded, CGKRK-modified lipid nanoparticles (C-SNPs) and demonstrated that C-SNPs could enrich in tumor cells and induce necroptosis in vitro and in vivo. Transcriptomic profiling revealed that C-SNPs suppressed tumor-cell mismatch repair, which later activated the cGAS-mediated IFN response and further increa

SUBMITTER: Yu S 

PROVIDER: S-EPMC12004912 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature