Increased response to TPF chemotherapy promotes immune escape in hypopharyngeal squamous cell carcinoma

• DOI: 10.3389/fphar.2022.1097197
• Publication Date: 2023-01-13T05:39:56Z
• Authors: Ruichen Li; Li Yan; Shu Tian; Yang Zhao; Yi Zhu; Xiaoshen Wang
• Keywords: E2F1

Background: There is an urgent need to identify which patients would benefit from TPF chemotherapy in hypopharyngeal squamous cell carcinoma (HPSCC) and explore new combinations improve the treatment effect. Materials methods: Gene-expression profiles 15 TPF-sensitive were compared 13 resistant patients. Immunohistochemistry (IHC) was performed detect CD8+ T cells 28 samples. Patient-Derived Tumor Xenograft (PDX) model IHC used verify markers that optimize for HPSCC. Results: Through RNA sequencing 188 genes up-regulated chemotherapy-resistant (CR) tissues involved activation, while 60 down-regulated glycolysis. Gene set enrichment analysis (GSEA) showed chemotherapy-sensitive (CS) group upregulation of pathways glycolysis, immune response downregulated. CIBERSORT, MCP-counter, proved most including CR significantly higher than CS group. Among 16 had close associations, significant negative correlation between gene level existed SEC61G. SEC61G related transcriptionally regulated by E2F1, participated antigen degradation through ubiquitin-dependent protein catabolic process. Palbociclib, combined with Cetuximab decreased tumor burden suppressed expression E2F1 activating MHC-I PDX model. Conclusion: Enhanced glycolysis promoted escape, but increased chemotherapy. center molecular network targeting E2F1/SEC61G pathway MHC-I.