Microenvironmental reorganization in brain tumors following radiotherapy and recurrence revealed by hyperplexed immunofluorescence imaging

Spencer S. Watson (), Benoit Duc, Ziqi Kang, Axel Tonnac, Nils Eling, Laure Font, Tristan Whitmarsh, Matteo Massara, Bernd Bodenmiller, Jean Hausser and Johanna A. Joyce ()
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Spencer S. Watson: University of Lausanne
Benoit Duc: University of Lausanne
Ziqi Kang: Karolinska Institutet and SciLifeLab
Axel Tonnac: Karolinska Institutet and SciLifeLab
Nils Eling: University of Zurich
Laure Font: University of Lausanne
Tristan Whitmarsh: University of Cambridge
Matteo Massara: University of Lausanne
Bernd Bodenmiller: University of Zurich
Jean Hausser: Karolinska Institutet and SciLifeLab
Johanna A. Joyce: University of Lausanne

Nature Communications, 2024, vol. 15, issue 1, 1-16

Abstract: Abstract The tumor microenvironment plays a crucial role in determining response to treatment. This involves a series of interconnected changes in the cellular landscape, spatial organization, and extracellular matrix composition. However, assessing these alterations simultaneously is challenging from a spatial perspective, due to the limitations of current high-dimensional imaging techniques and the extent of intratumoral heterogeneity over large lesion areas. In this study, we introduce a spatial proteomic workflow termed Hyperplexed Immunofluorescence Imaging (HIFI) that overcomes these limitations. HIFI allows for the simultaneous analysis of > 45 markers in fragile tissue sections at high magnification, using a cost-effective high-throughput workflow. We integrate HIFI with machine learning feature detection, graph-based network analysis, and cluster-based neighborhood analysis to analyze the microenvironment response to radiation therapy in a preclinical model of glioblastoma, and compare this response to a mouse model of breast-to-brain metastasis. Here we show that glioblastomas undergo extensive spatial reorganization of immune cell populations and structural architecture in response to treatment, while brain metastases show no comparable reorganization. Our integrated spatial analyses reveal highly divergent responses to radiation therapy between brain tumor models, despite equivalent radiotherapy benefit.

Date: 2024
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DOI: 10.1038/s41467-024-47185-9

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