Scheuermann, Sophia; Kristmann, Beate; Engelmann, Fabienne; Nuernbergk, Alice; Scheuermann, David; Koloseus, Marie; Abed, Tayeb; Solass, Wiebke; Seitz, Christian M (2024). Unveiling spatial complexity in solid tumor immune microenvironments through multiplexed imaging. Frontiers in immunology, 15(1383932) Frontiers Research Foundation 10.3389/fimmu.2024.1383932
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Deciphering cellular components and the spatial interaction network of the tumor immune microenvironment (TIME) of solid tumors is pivotal for understanding biologically relevant cross-talks and, ultimately, advancing therapies. Multiplexed tissue imaging provides a powerful tool to elucidate spatial complexity in a holistic manner. We established and cross-validated a comprehensive immunophenotyping panel comprising over 121 markers for multiplexed tissue imaging using MACSima™ imaging cyclic staining (MICS) alongside an end-to-end analysis workflow. Applying this panel and workflow to primary cancer tissues, we characterized tumor heterogeneity, investigated potential therapeutical targets, conducted in-depth profiling of cell types and states, sub-phenotyped T cells within the TIME, and scrutinized cellular neighborhoods of diverse T cell subsets. Our findings highlight the advantage of spatial profiling, revealing immunosuppressive molecular signatures of tumor-associated myeloid cells interacting with neighboring exhausted, PD1high T cells in the TIME of hepatocellular carcinoma (HCC). This study establishes a robust framework for spatial exploration of TIMEs in solid tumors and underscores the potency of multiplexed tissue imaging and ultra-deep cell phenotyping in unraveling clinically relevant tumor components.
Item Type: |
Journal Article (Original Article) |
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Division/Institute: |
04 Faculty of Medicine > Service Sector > Institute of Pathology > Clinical Pathology 04 Faculty of Medicine > Service Sector > Institute of Pathology |
UniBE Contributor: |
Solass, Wiebke |
Subjects: |
600 Technology > 610 Medicine & health |
ISSN: |
1664-3224 |
Publisher: |
Frontiers Research Foundation |
Language: |
English |
Submitter: |
Pubmed Import |
Date Deposited: |
03 Apr 2024 15:26 |
Last Modified: |
04 Apr 2024 03:48 |
Publisher DOI: |
10.3389/fimmu.2024.1383932 |
PubMed ID: |
38566984 |
Uncontrolled Keywords: |
MACSima™ multiplexed tissue imaging single-cell analysis spatial analysis workflow tumor immunophenotyping tumor microenvironment (TME) |
BORIS DOI: |
10.48350/195636 |
URI: |
https://boris.unibe.ch/id/eprint/195636 |