A critical limitation of immunotherapy in GBM is the highly immunosuppressive nature of the TME, which actively restricts T cell infiltration and function.485 A dysfunctional BBB exacerbates this issue by permitting the secretion of immunosuppressive cytokines such as TGF-β and IL-10 while promoting the accumulation of MDSCs and TAMs, both of which inhibit immune activation.316 To overcome these barriers, ICIs combined with TME-modulating agents, such as CSF-1R inhibitors and anti-TGF-β therapies, are being explored. The gene discussed is TGFB1; the disease is glioblastoma.