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

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, David Henderson, Ji Shi, Yi Liu, Heikki Joensuu, Henrik Lindman, Roberto A. Leon-Ferre, Judy C. Boughey, Minetta C. Liu, James N. Ingle, Krishna R. Kalari, Fergus J. Couch, Keith L. Knutson, Matthew P. Goetz, Edith A. Perez and E. Aubrey Thompson ()
Additional contact information
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

Nature Communications, 2023, vol. 14, issue 1, 1-14

Abstract: 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.

Date: 2023
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DOI: 10.1038/s41467-023-37806-0

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