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Introduction: Abundance of immune cells has been shown to have prognostic and predictive significance in many tumor types. Beyond abundance, the spatial organization of immune cells in relation to cancer cells may also have significant functional and clinical implications. However there

Introduction: Abundance of immune cells has been shown to have prognostic and predictive significance in many tumor types. Beyond abundance, the spatial organization of immune cells in relation to cancer cells may also have significant functional and clinical implications. However there is a lack of systematic methods to quantify spatial associations between immune and cancer cells.

Methods: We applied ecological measures of species interactions to digital pathology images for investigating the spatial associations of immune and cancer cells in breast cancer. We used the Morisita-Horn similarity index, an ecological measure of community structure and predator–prey interactions, to quantify the extent to which cancer cells and immune cells colocalize in whole-tumor histology sections. We related this index to disease-specific survival of 486 women with breast cancer and validated our findings in a set of 516 patients from different hospitals.

Results: Colocalization of immune cells with cancer cells was significantly associated with a disease-specific survival benefit for all breast cancers combined. In HER2-positive subtypes, the prognostic value of immune-cancer cell colocalization was highly significant and exceeded those of known clinical variables. Furthermore, colocalization was a significant predictive factor for long-term outcome following chemotherapy and radiotherapy in HER2 and Luminal A subtypes, independent of and stronger than all known clinical variables.

Conclusions: Our study demonstrates how ecological methods applied to the tumor microenvironment using routine histology can provide reproducible, quantitative biomarkers for identifying high-risk breast cancer patients. We found that the clinical value of immune-cancer interaction patterns is highly subtype-specific but substantial and independent to known clinicopathologic variables that mostly focused on cancer itself. Our approach can be developed into computer-assisted prediction based on histology samples that are already routinely collected.

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    Title
    • An Ecological Measure of Immune-Cancer Colocalization as a Prognostic Factor for Breast Cancer
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    Date Created
    2015-09-22
    Resource Type
  • Text
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    Identifier
    • Digital object identifier: 10.1186/s13058-015-0638-4
    • Identifier Type
      International standard serial number
      Identifier Value
      1465-542X
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    • The electronic version of this article is the complete one and can be found online at: https://breast-cancer-research.biomedcentral.com/articles/10.1186/s13058-015-0638-4

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    This is a suggested citation. Consult the appropriate style guide for specific citation guidelines.

    Maley, C. C., Koelble, K., Natrajan, R., Aktipis, A., & Yuan, Y. (2015). An ecological measure of immune-cancer colocalization as a prognostic factor for breast cancer. Breast Cancer Research, 17(1). doi:10.1186/s13058-015-0638-4

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