INSERM U932, PSL University, Institut Curie, Paris, France.
Laboratoire d'immunologie clinique, Institut Curie, Paris, France.
Cancer Immunol Res. 2022 Jul 1;10(7):800-810. doi: 10.1158/2326-6066.CIR-21-1050.
Glioblastoma (GBM) is an immunologically "cold" tumor characterized by poor responsiveness to immunotherapy. Standard of care for GBM is surgical resection followed by chemoradiotherapy and maintenance chemotherapy. However, tumor recurrence is the norm, and recurring tumors are found frequently 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. See related Spotlight by Bayik et al., p. 787.
胶质母细胞瘤（GBM）是一种免疫“冷”肿瘤，其对免疫疗法的反应较差。GBM 的标准治疗方法是手术切除，然后进行放化疗和维持化疗。然而，肿瘤复发是常态，并且复发的肿瘤经常获得可能影响其免疫生物学的分子变化（例如，突变）。在这里，我们使用高维细胞术和多重免疫组化比较了初发性 GBM 和复发性 GBM（rGBM）的免疫结构。尽管初发性和 rGBM 中的髓样细胞和 T 细胞同样丰富，但它们在肿瘤内的空间组织不同，并且与结局相关。在 rGBM 中，T 细胞在血管周围区域富集并被激活，并与激活的巨噬细胞和较少的调节性 T 细胞聚集在一起。此外，在复发时这些区域 T 细胞中磷酸化 STAT1 的表达较高与预后良好相关。总之，我们的数据确定了初发性 GBM 和 rGBM 的免疫生物学的差异，并确定了血管周围 T 细胞作为潜在的治疗靶点。请参阅相关的 Spotlight 文章，由 Bayik 等人撰写，第 787 页。
