Abstract
IntroductionAbundance 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.MethodsWe 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.ResultsColocalization 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.ConclusionsOur 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s13058-015-0638-4) contains supplementary material, which is available to authorized users.
Highlights
Abundance of immune cells has been shown to have prognostic and predictive significance in many tumor types
Immune-cancer cell colocalization was independent of known parameters of breast cancer hematoxylin and eosin (H&E)-stained tumor section images representing 1002 primary breast tumors were analyzed using our image analysis tool to identify cancer cells and immune cells based on their morphology (Fig. 1a-b, Table 1, Additional file 1)
Immune-cancer cell colocalization is associated with a good prognosis in human epidermal growth factor receptor 2 (Her2)+ and luminal A tumors We investigated the association between colocalization with the intrinsic molecular subtypes defined by the PAM50 gene set
Summary
Abundance of immune cells has been shown to have prognostic and predictive significance in many tumor types. We discovered that dense concentrations (“hotspots”) formed by both immune and cancer cells, rather than those formed by one cell type alone, are associated with good prognosis in estrogen receptor (ER)-negative breast cancer [16]. This highlights the importance of investigating how cancer and immune cells are spatially related and raises the question: can we characterize the spatial association between cancer and immune cells and thereby elucidate the ecological dynamics that could influence tumor progression and response to treatment?
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
