Immunologic Features in De Novo and Recurrent Glioblastoma Are Associated with Survival Outcomes

Glioblastoma (GBM) is an immunologically cold tumor characterized by poor responsiveness to immunotherapy. Stan-dard of care for GBM is surgical resection followed by chemo-radiotherapy and maintenance chemotherapy. However, tumor recurrence is the norm, and recurring tumors are found fre-quently to have acquired molecular changes (e.g., mutations) that may influence their immunobiology. Here, we compared the immune contexture of de novo GBM and recurrent GBM (rGBM) using high-dimensional cytometry and multiplex IHC. Although myeloid and T cells were similarly abundant in de novo and rGBM, their spatial organization within tumors differed and was linked to outcomes. In rGBM, T cells were enriched and activated in perivascular regions and clustered with activated macrophages and fewer regulatory T cells. Moreover, a higher expression of phosphorylated STAT1 by T cells in these regions at recurrence was associated with a favorable prognosis. Together, our data identify differences in the immunobiology of de novo GBM and rGBM and identify perivascular T cells as potential therapeutic targets.

Automated summary

The study found that T cells in the perivascular regions of recurrent GBM were enriched and activated, and their presence was associated with outcomes, indicating that these T cells may be potential therapeutic targets.