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Cell. 2018 Sep 6;174(6):1373-1387.e19. doi: 10.1016/j.cell.2018.08.039.

A Structured Tumor-Immune Microenvironment in Triple Negative Breast Cancer Revealed by Multiplexed Ion Beam Imaging.

Author information

1
Department of Pathology, Stanford University, Stanford CA, 94305, USA.
2
Department of Biology, Caltech, Pasadena, CA 91125, USA; Department of Bioengineering, Caltech, Pasadena, CA 91125, USA.
3
Department of Pathology, Stanford University, Stanford CA, 94305, USA. Electronic address: bendall@stanford.edu.
4
Department of Pathology, Stanford University, Stanford CA, 94305, USA. Electronic address: mangelo0@stanford.edu.

Abstract

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:

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

PMID:
30193111
PMCID:
PMC6132072
[Available on 2019-09-06]
DOI:
10.1016/j.cell.2018.08.039

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