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Protein-based immune profiles of basal-like vs. luminal breast cancers

Laboratory Investigation (2021)Cite this article

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Abstract

Tumor-infiltrating lymphocytes play an important, but incompletely understood role in chemotherapy response and prognosis. In breast cancer, there appear to be distinct immune responses by subtype, but most studies have used limited numbers of protein markers or bulk sequencing of RNA to characterize immune response, in which spatial organization cannot be assessed. To identify immune phenotypes of Basal-like vs. Luminal breast cancer we used the GeoMx® (NanoString) platform to perform digital spatial profiling of immune-related proteins in tumor whole sections and tissue microarrays (TMA). Visualization of CD45, CD68, or pan-Cytokeratin by immunofluorescence was used to select regions of interest in formalin-fixed paraffin embedded tissue sections. Forty-four antibodies representing stromal markers and multiple immune cell types were applied to quantify the tumor microenvironment. In whole tumor slides, immune hot spots (CD45+) had increased expression of many immune markers, suggesting a diverse and robust immune response. In epithelium-enriched areas, immune signals were also detectable and varied by subtype, with regulatory T-cell (Treg) markers (CD4, CD25, and FOXP3) being higher in Basal-like vs. Luminal breast cancer. Extending these findings to TMAs with more patients (n = 75), we confirmed subtype-specific immune profiles, including enrichment of Treg markers in Basal-likes. This work demonstrated that immune responses can be detected in epithelium-rich tissue, and that TMAs are a viable approach for obtaining important immunoprofiling data. In addition, we found that immune marker expression is associated with breast cancer subtype, suggesting possible prognostic, or targetable differences.

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Fig. 1: Subtype immune marker heterogeneity is apparent in epithelium-enriched regions versus immune hot spots.
Fig. 2: Treg marker expression is higher in Basal-like tumors.

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Acknowledgements

Thank you to the Lineberger Comprehensive Cancer Center, a Cancer Center Support Grant (P30 CA016086), the UNC-CH Cancer Control Education Program (5T32CA057726-28), Susan G Komen for the Cure (OGUNC1202), the North Carolina University Cancer Research Fund, and the NCI-funded UNC Breast SPORE (P50 CA058223). Thank you to Liang and Erica from Nanostring. We would also like to thank the CBCS participants and staff. We also want to acknowledge Robert C. Millikan, founder of the CBCS Phase 3.

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Affiliations

  1. Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, 27599, USA

    Andrea Walens, Xiaohua Gao, Stephanie M. Cohen, Bentley R. Midkiff, Yongjuan Xia, Nana Nikolaishvili-Feinberg, Jonathan S. Serody, Katherine A. Hoadley, Melissa A. Troester & Benjamin C. Calhoun

  2. Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, 27599, USA

    Andrea Walens, Linnea T. Olsson, Xiaohua Gao, Erin L. Kirk & Melissa A. Troester

  3. Department of Pathology and Laboratory Medicine, School of Medicine, University of North Carolina, Chapel Hill, NC, 27599, USA

    Alina M. Hamilton, Melissa A. Troester & Benjamin C. Calhoun

  4. Translational Pathology Laboratory, University of North Carolina School of Medicine, Chapel Hill, NC, 27599, USA

    Stephanie M. Cohen, Bentley R. Midkiff, Yongjuan Xia & Nana Nikolaishvili-Feinberg

  5. Health Sciences Research, Mayo Clinic, Jacksonville, FL, 32224, USA

    Mark E. Sherman

  6. Division of Hematology, Department of Medicine, University of North Carolina, Chapel Hill, NC, 27599, USA

    Jonathan S. Serody

  7. Department of Microbiology and Immunology, University of North Carolina, Chapel Hill, NC, 27599, USA

    Jonathan S. Serody

  8. Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA

    Katherine A. Hoadley

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  1. Andrea Walens
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Correspondence to Melissa A. Troester or Benjamin C. Calhoun.

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BCC is a member of the Oncology Advisory Board for Luminex Corp.

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Walens, A., Olsson, L.T., Gao, X. et al. Protein-based immune profiles of basal-like vs. luminal breast cancers. Lab Invest (2021). https://doi.org/10.1038/s41374-020-00506-0

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