Cell
Volume 174, Issue 6, 6 September 2018, Pages 1373-1387.e19
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Article
A Structured Tumor-Immune Microenvironment in Triple Negative Breast Cancer Revealed by Multiplexed Ion Beam Imaging

https://doi.org/10.1016/j.cell.2018.08.039Get rights and content
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Highlights

  • Multiplexed Imaging of subcellular expression of 36 proteins in 41 TNBC patients

  • Enriched co-occurrence of immune populations defines a structured immune environment

  • Tumor infiltration by immune cells varies from compartmentalized to mixed patients

  • Expression of PD-1 and PD-L1 by distinct cells relate to tumor histology and survival

Summary

The immune system is critical in modulating cancer progression, but knowledge of immune composition, phenotype, and interactions with tumor is limited. We used multiplexed ion beam imaging by time-of-flight (MIBI-TOF) to simultaneously quantify in situ expression of 36 proteins covering identity, function, and immune regulation at sub-cellular resolution in 41 triple-negative breast cancer patients. Multi-step processing, including deep-learning-based segmentation, revealed variability in the composition of tumor-immune populations across individuals, reconciled by overall immune infiltration and enriched co-occurrence of immune subpopulations and checkpoint expression. Spatial enrichment analysis showed immune mixed and compartmentalized tumors, coinciding with expression of PD1, PD-L1, and IDO in a cell-type- and location-specific manner. Ordered immune structures along the tumor-immune border were associated with compartmentalization and linked to survival. These data demonstrate organization in the tumor-immune microenvironment that is structured in cellular composition, spatial arrangement, and regulatory-protein expression and provide a framework to apply multiplexed imaging to immune oncology.

Keywords

Tumor Microenvironment
Tumor Immunology
Imaging
Breast Cancer
Checkpoint
MIBI
Multiplexed Ion Beam Imaging
Mass spectrometry
Proteomics
Systems Biology

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