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Distinct spatial immune microlandscapes are independently associated with outcomes in triple-negative breast cancer

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Listed:
  • Jodi M. Carter

    (University of Alberta)

  • Saranya Chumsri

    (Division of Hematology and Oncology, Mayo Clinic)

  • Douglas A. Hinerfeld

    (Ultima Genomics)

  • Yaohua Ma

    (Division of Biomedical Statistics and Informatics, Mayo Clinic)

  • Xue Wang

    (Division of Biomedical Statistics and Informatics, Mayo Clinic)

  • David Zahrieh

    (Division of Biomedical Statistics and Informatics, Mayo Clinic)

  • David W. Hillman

    (Division of Biomedical Statistics and Informatics, Mayo Clinic)

  • Kathleen S. Tenner

    (Division of Biomedical Statistics and Informatics, Mayo Clinic)

  • Jennifer M. Kachergus

    (Department of Cancer Biology, Mayo Clinic)

  • Heather Ann Brauer

    (Bill and Melinda Gates Foundation)

  • Sarah E. Warren

    (Kite Pharma)

  • David Henderson

    (NanoString Technologies, Inc)

  • Ji Shi

    (Department of Cancer Biology, Mayo Clinic)

  • Yi Liu

    (Department of Cancer Biology, Mayo Clinic)

  • Heikki Joensuu

    (Helsinki University Hospital and University of Helsinki)

  • Henrik Lindman

    (University of Uppsala)

  • Roberto A. Leon-Ferre

    (Division of Medical Oncology, Mayo Clinic)

  • Judy C. Boughey

    (Department of Surgery, Mayo Clinic)

  • Minetta C. Liu

    (Natera, Inc)

  • James N. Ingle

    (Division of Medical Oncology, Mayo Clinic)

  • Krishna R. Kalari

    (Division of Biomedical Statistics and Informatics, Mayo Clinic)

  • Fergus J. Couch

    (Department of Laboratory Medicine and Pathology, Mayo Clinic)

  • Keith L. Knutson

    (Department of Immunology, Mayo Clinic)

  • Matthew P. Goetz

    (Division of Medical Oncology, Mayo Clinic)

  • Edith A. Perez

    (Division of Hematology and Oncology, Mayo Clinic)

  • E. Aubrey Thompson

    (Department of Cancer Biology, Mayo Clinic)

Abstract

The utility of spatial immunobiomarker quantitation in prognostication and therapeutic prediction is actively being investigated in triple-negative breast cancer (TNBC). Here, with high-plex quantitative digital spatial profiling, we map and quantitate intraepithelial and adjacent stromal tumor immune protein microenvironments in systemic treatment-naïve (female only) TNBC to assess the spatial context in immunobiomarker-based prediction of outcome. Immune protein profiles of CD45-rich and CD68-rich stromal microenvironments differ significantly. While they typically mirror adjacent, intraepithelial microenvironments, this is not uniformly true. In two TNBC cohorts, intraepithelial CD40 or HLA-DR enrichment associates with better outcomes, independently of stromal immune protein profiles or stromal TILs and other established prognostic variables. In contrast, intraepithelial or stromal microenvironment enrichment with IDO1 associates with improved survival irrespective of its spatial location. Antigen-presenting and T-cell activation states are inferred from eigenprotein scores. Such scores within the intraepithelial compartment interact with PD-L1 and IDO1 in ways that suggest prognostic and/or therapeutic potential. This characterization of the intrinsic spatial immunobiology of treatment-naïve TNBC highlights the importance of spatial microenvironments for biomarker quantitation to resolve intrinsic prognostic and predictive immune features and ultimately inform therapeutic strategies for clinically actionable immune biomarkers.

Suggested Citation

  • Jodi M. Carter & Saranya Chumsri & Douglas A. Hinerfeld & Yaohua Ma & Xue Wang & David Zahrieh & David W. Hillman & Kathleen S. Tenner & Jennifer M. Kachergus & Heather Ann Brauer & Sarah E. Warren & , 2023. "Distinct spatial immune microlandscapes are independently associated with outcomes in triple-negative breast cancer," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
  • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-37806-0
    DOI: 10.1038/s41467-023-37806-0
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