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Biology subjects

Hoebel, K.

Publications and source records attributed to Hoebel, K..

2 recordsLinked to original sources

Pan-cancer spatial characterization of key immune biomarkers in the tumor microenvironment

Deciphering the composition and spatial organization of the tumor immune microenvironment (TiME) is key to uncovering the mechanisms driving cancer progression and treatment response. Spatial biology techniques like multiplex immunofluorescence (mIF) offer detailed insights into the TiME but are often limited to retrospective research studies of individual cancer types. Conversely, bulk omics techniques have been studied in pan-cancer settings but fail to capture single-cell spatial information. Here, we provide a pan-cancer spatial characterization of key biomarkers (CD8, FOXP3, PD-1, PD-L1) of the TiME using data from a mIF assay performed prospectively in a clinical setting on 2,019 tumors across 14 major cancer types. By integrating interpretable compositional and spatial metrics, we identified patterns of TiME variation that are conserved across cancer types and stages. We assess associations between these TiME spatial factors and tumor, genomic, and clinical features, where the results both extend prior findings and uncover new links. Altogether, our findings offer pan-cancer insights of the TiME to further the fields of spatial biology and cancer immunology.

cancer biology↗

Structural and functional vascular dysfunction within brain metastases is linked to pembrolizumab inefficacy

Structurally and functionally aberrant vasculature is a hallmark of tumor angiogenesis and treatment resistance. Given the synergistic link between aberrant tumor vasculature and immunosuppression, we analyzed perfusion MRI for 44 patients with brain metastases (BM) undergoing treatment with pembrolizumab. To date, vascular-immune communication, or the relationship between immune checkpoint inhibitor (ICI) efficacy and vascular architecture, has not been well-characterized in human imaging studies. We found that ICI-responsive BM possessed a structurally balanced vascular makeup, which was linked to improved vascular efficiency and an immune-stimulatory microenvironment. In contrast, ICI-resistant BM were characterized by a lack of immune cell infiltration and a highly aberrant vasculature dominated by large-caliber vessels. Peri-tumor region analysis revealed early functional changes predictive of ICI resistance before radiographic evidence on conventional MRI. This study was one of the largest functional imaging studies for BM and establishes a foundation for functional studies that illuminate the mechanisms linking patterns of vascular architecture with immunosuppression, as targeting these aspects of cancer biology may serve as the basis for future combination treatments.

cancer biology↗