Single-cell heterogeneity of EGFR and CDK4 co-amplification is linked to immune infiltration in glioblastoma.

Single-cell heterogeneity of EGFR and CDK4 co-amplification is linked to immune infiltration in glioblastoma.
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DOI:
10.1016/j.celrep.2023.112235
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发表时间:
2023-03-28
期刊:
影响因子:
8.8
通讯作者:
--
中科院分区:
生物学1区
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--
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Glioblastoma (GBM) is the most aggressive brain tumor, with a median survival of ~15 months. Targeted approaches have not been successful in this tumor type due to the large extent of intratumor heterogeneity. Mosaic amplification of oncogenes suggests that multiple genetically distinct clones are present in each tumor. To uncover the relationships between genetically diverse subpopulations of GBM cells and their native tumor microenvironment, we employ highly multiplexed spatial protein profiling coupled with single-cell spatial mapping of fluorescence in situ hybridization (FISH) for EGFR, CDK4, and PDGFRA. Single-cell FISH analysis of a total of 35,843 single nuclei reveals that tumors in which amplifications of EGFR and CDK4 more frequently co-occur in the same cell exhibit higher infiltration of CD163+ immunosuppressive macrophages. Our results suggest that high-throughput assessment of genomic alterations at the single-cell level could provide a measure for predicting the immune state of GBM. Glioblastoma cellular diversity in the context of tumor tissue microenvironments remains poorly understood. Walentynowicz et al. use the relative frequency of cells harboring co-amplification of EGFR and CDK4 to classify tumors and show that the presence of genetically distinct subpopulations is associated with differences in immunosuppressive macrophage infiltration in glioblastoma tissue.
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