@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"
 }