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This UCSF preclinical study implicates IL-6 as an important regulator of the glioblastoma (GBM) immune microenvironment. Using integrated spatial and single-cell analyses of patient-matched human GBM samples, the authors show that lower baseline IL-6 is associated with the rare clinical responses seen with immune checkpoint inhibitors (ICIs), while higher IL-6 correlates with poorer outcomes. These findings are consistent with prior observations by Dr. Steven Brem and others linking IL-6 to immune suppression and prognosis in GBM. In preclinical models, IL-6 blockade alone was not sufficient for durable tumor control, but it shifted the tumor immune microenvironment by reducing regulatory T cells and increasing antigen presentation and effector CD8+ T-cell activity. When combined with immune checkpoint inhibition and radiotherapy, IL-6 blockade translated into more durable anti-tumor responses. This work further supports a combination strategy where targeting cytokine-driven resistance pathways may help overcome immunotherapy resistance in GBM.