@ARTICLE{keren2018,
  title     = "A structured tumor-immune microenvironment in triple negative
               breast cancer revealed by multiplexed ion beam imaging",
  author    = "Keren, L and Bosse, M and Marquez, D and Angoshtari,
               R and Jain, S and Varma, S and Yang, S and
               Kurian, A and Van Valen, D and West, R and
               Bendall, S C and Angelo, M",
  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.",
  journal   = "Cell",
  publisher = "Elsevier BV",
  volume    =  174,
  number    =  6,
  pages     = "1373--1387.e19",
  month     =  sep,
  year      =  2018,
  keywords  = "Breast Cancer; Checkpoint; Imaging; MIBI; Mass spectrometry;
               Multiplexed Ion Beam Imaging; Proteomics; Systems Biology; Tumor
               Immunology; Tumor Microenvironment",
  copyright = "http://www.elsevier.com/open-access/userlicense/1.0/",
  language  = "en"
}
