Hyperglycemia promotes tumor immune evasion via B7-H4 upregulation in ovarian cancer
The efficacy of ICB therapy has long been shown to be less prominent in patients with metabolic disorders, including type II diabetes, but the underlying mechanisms remain unclear. To investigate how hyperglycemia influences tumor immune evasion and suppresses CD8 The BKS db/db mice, a model of type II diabetes, and ID8 ovarian cancer cells were used to evaluate tumor growth, immune cell infiltration, and the impact of hyperglycemia on immune checkpoint expression. Flow cytometry, Western blotting, and chromatin immunoprecipitation (ChIP) assays were performed to explore the molecular mechanisms linking hyperglycemia to B7-H4 upregulation. Accelerated tumor growth and reduced responsiveness to ICB therapy were observed in BKS db/db mice in comparison to wild-type controls. Tumors from hyperglycemic mice exhibited significantly higher expression of B7-H4 due to reduced CD8 This study reveals that hyperglycemia promotes tumor immune evasion through AP-1-mediated B7-H4 upregulation in ovarian cancer cells, resulting in impaired CD8