A Structured Tumor-Immune Microenvironment in Triple Negative Breast Cancer Revealed by Multiplexed Ion Beam Imaging
By Leeat Keren, M. Bosse, Diana Marquez, Roshan Angoshtari, Samir Jain, S. Varma, Soo-Ryum Yang, A. Kurian, D. V. Valen, Robert West and 2 more. Cell, 2018
1,009 citations recorded by the source corpus.
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.
Subfields: Immunology, Oncology
View Paper: https://www.semanticscholar.org/paper/4d220b660fa6be683491af5489ef6f180986f8d3
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Citations in the corpus
- Evaluation of Deep Learning Strategies for Nucleus Segmentation in Fluorescence Images (2018, background): “For instance, analyzing the structure of tumors in tissues using multiplexed ion beam imaging reveals the spatial organization and response of immune cells in cancer patients (50).”
- MIBI-TOF: A multiplexed imaging platform relates cellular phenotypes and tissue structure (2019, methodology): “In previous work, we used MIBITOF to characterize the tumor immune microenvironment in a cohort of 41 triple-negative breast cancer (TNBC) patients and found connections between the presence and organization of specific immune cell types and overall survival (26).”
- Tertiary lymphoid structures in cancer (2022, background): “As a first example, an analysis of immune infiltrates in breast cancer has revealed that tumors with comparable immune infiltrates displayed distinct spatial distributions, referred to as mixed and compartmentalized organization (12).”
- Intratumor heterogeneity: the Rosetta stone of therapy resistance (2020, background): “Based on the frequency and location of immune cells tumors can be classified as immune cold (immune desert), peritumoral, stromal-restricted, and inflamed (Gruosso et al., 2019; Keren et al., 2018; Rosenthal et al., 2019).”
- Spatial components of molecular tissue biology (2022, positive): “Several recent studies follow this approach in conditions as diverse as cancer 34,35,85–89 , myocardial infarction 90 and neurodegenerative diseases 91 .”
- Coordinated Cellular Neighborhoods Orchestrate Antitumoral Immunity at the Colorectal Cancer Invasive Front (2019, background): “Focusing on the iTME, other investigators applying multiplexed imaging have explored cellular functional states, spatial and functional interactions between multiple cell types, as well as how these interactions are modulated by tissue context (Ali et al., 2020; Arnol et al., 2019; Jackson et al., 2”