肿瘤进化是由遗传变异驱动的；然而，肿瘤微环境（TME）提供了促进癌症进化的选择压力。尽管胶质母细胞瘤 (GBM) 这种最具侵袭性的脑肿瘤具有高度的组织病理学异质性，但遗传上不同的 GBM 细胞与周围 TME 之间的相互作用尚不完全清楚。为了解决这个问题，我们利用基于成像的技术分析了匹配的原发性和复发性 GBM 档案肿瘤组织，旨在同时评估肿瘤组织是否存在缺氧、血管生成和炎症生态位、细胞外基质组织、TERT 启动子突变状态以及几种致癌扩增。相同的幻灯片和位置。我们发现，在原发性肿瘤和相匹配的复发性肿瘤中，遗传和 TME 多样性之间的关系是不同的。有趣的是，通过无标记反射成像识别的细胞外基质（ECM）的纹理可以预测组织中存在的单细胞遗传特征。此外，ECM 的反射揭示了复发性 GBM 中血管周围生态位的结构化组织，富含免疫抑制性巨噬细胞。单细胞空间转录组学进一步证实了生态位特异性巨噬细胞群的存在，并确定了内皮细胞、血管周围成纤维细胞和免疫抑制巨噬细胞之间的相互作用。我们的结果强调了 GBM 组织组织在肿瘤进化中的重要性，并强调了新的遗传和空间依赖性。

Tumor evolution is driven by genetic variation; however, it is the tumor microenvironment (TME) that provides the selective pressure contributing to evolution in cancer. Despite high histopathological heterogeneity within glioblastoma (GBM), the most aggressive brain tumor, the interactions between the genetically distinct GBM cells and the surrounding TME are not fully understood. To address this, we analyzed matched primary and recurrent GBM archival tumor tissues with imaging-based techniques aimed to simultaneously evaluate tumor tissues for presence of hypoxic, angiogenic, and inflammatory niches, extracellular matrix organization, TERT promoter mutational status, and several oncogenic amplifications on the same slide and location. We found that the relationships between genetic and TME diversity are different in primary and matched recurrent tumors. Interestingly, the texture of the extracellular matrix (ECM), identified by label-free reflectance imaging, was predictive of single-cell genetic traits present in the tissue. Moreover, reflectance of ECM revealed structured organization of the perivascular niche in recurrent GBM, enriched in immunosuppressive macrophages. Single-cell spatial transcriptomics further confirmed the presence of the niche-specific macrophage populations and identified interactions between endothelial cells, perivascular fibroblasts, and immunosuppressive macrophages. Our results underscore the importance of GBM tissue organization in tumor evolution and highlight novel genetic and spatial dependencies.