. 2015 Jan; 95(4):377-84.
doi: 10.1038/labinvest.2014.155.

Mapping spatial heterogeneity in the tumor microenvironment: a new era for digital pathology

Andreas Heindl 1 Sidra Nawaz 1 Yinyin Yuan 1 
  • PMID: 25599534
  •     53 References
  •     67 citations


The emergent field of digital pathology employing automated image analysis techniques is to revolutionize traditional pathology at the center of clinical diagnostics. Histological images provide important tumor features unavailable in molecular profiling or omics data- the spatial context of tumor and stromal cells at single-cell resolution. Methods to map the spatial and morphological patterns of cancer and normal cells can contribute to a more comprehensive understanding of the highly heterogeneous tumor microenvironment. This review focuses on methods that help expand our knowledge of intra-tumoral spatial heterogeneity of the tumor microenvironment and their potential synergies with molecular profiling technologies.

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Quantification of spatial tumor heterogeneity in immunohistochemistry staining images.
Inna Chervoneva, Amy R Peck, +2 authors, Hallgeir Rui.
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Distinct Patterns of Myeloid Cell Infiltration in Patients With hrHPV-Positive and hrHPV-Negative Penile Squamous Cell Carcinoma: The Importance of Assessing Myeloid Cell Densities Within the Spatial Context of the Tumor.
Tynisha S Rafael, Hielke M de Vries, +8 authors, Oscar R Brouwer.
Front Immunol, 2021 Jul 02; 12. PMID: 34194435    Free PMC article.
Biologically-Based Mathematical Modeling of Tumor Vasculature and Angiogenesis via Time-Resolved Imaging Data.
David A Hormuth, Caleb M Phillips, +6 authors, Thomas E Yankeelov.
Cancers (Basel), 2021 Jul 03; 13(12). PMID: 34208448    Free PMC article.
A Spatial Quantitative Systems Pharmacology Platform spQSP-IO for Simulations of Tumor-Immune Interactions and Effects of Checkpoint Inhibitor Immunotherapy.
Chang Gong, Alvaro Ruiz-Martinez, Holly Kimko, Aleksander S Popel.
Cancers (Basel), 2021 Aug 08; 13(15). PMID: 34359653    Free PMC article.
Uncovering Spatiotemporal Heterogeneity of High-Grade Gliomas: From Disease Biology to Therapeutic Implications.
Andrea Comba, Syed M Faisal, +7 authors, Pedro R Lowenstein.
Front Oncol, 2021 Aug 24; 11. PMID: 34422657    Free PMC article.
Unraveling Tumor Heterogeneity by Using DNA Barcoding Technologies to Develop Personalized Treatment Strategies in Advanced-Stage PDAC.
Philip Dujardin, Anna K Baginska, Sebastian Urban, Barbara M Grüner.
Cancers (Basel), 2021 Aug 28; 13(16). PMID: 34439341    Free PMC article.
Systemic Inflammation Associates With a Myeloid Inflamed Tumor Microenvironment in Primary Resected Colon Cancer-May Cold Tumors Simply Be Too Hot?
Anne Helene Køstner, Patricia Switten Nielsen, +4 authors, Torben Steiniche.
Front Immunol, 2021 Sep 18; 12. PMID: 34531864    Free PMC article.
Breast Cancer Heterogeneity.
Caterina Fumagalli, Massimo Barberis.
Diagnostics (Basel), 2021 Sep 29; 11(9). PMID: 34573897    Free PMC article.
Digital pathology and artificial intelligence in translational medicine and clinical practice.
Vipul Baxi, Robin Edwards, Michael Montalto, Saurabh Saha.
Mod Pathol, 2021 Oct 07;. PMID: 34611303    Free PMC article.
Predictive models of response to neoadjuvant chemotherapy in muscle-invasive bladder cancer using nuclear morphology and tissue architecture.
Haoyang Mi, Trinity J Bivalacqua, +4 authors, Alexander S Baras.
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