A structured tumor-immune microenvironment in triple negative breast cancer revealed by multiplexed ion beam imaging

• Leeat Keren ^[1] ; Marc Bosse ^[2] ; Diana Marquez ^[1]
  1. [1] Stanford University

     Stanford University

     Estados Unidos

     
  2. [2] Stanfor University
• Localización: Cell, ISSN 0092-8674, Vol. 174, Nº. 6, 2018, págs. 1373-1387
• Idioma: inglés
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• Resumen

  • 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.