Second, targeting the unique immune microenvironment of glioma, recent studies have proposed a “NETs‐HMGB1/RAGE/IL‐8‐CXCR2” positive feedback loop, demonstrating that RAGE inhibitors, CXCR2 antagonists, or PI3K/AKT inhibitors can effectively disrupt this loop [157], providing a theoretical basis for combining HMGB1‐targeted therapy with immunomodulatory strategies. The gene discussed is CXCR2; the disease is glioma.