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; E. Aubrey Thompson

doi:10.1038/s41467-023-37806-0

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. IngleKrishna R. Kalari, Fergus J. Couch, Keith L. Knutson, Matthew P. Goetz, Edith A. Perez, E. Aubrey Thompson

Research output: Contribution to journal › Article › peer-review

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.

Original language	English (US)
Article number	2215
Journal	Nature communications
Volume	14
Issue number	1
DOIs	https://doi.org/10.1038/s41467-023-37806-0
State	Published - Dec 2023

ASJC Scopus subject areas

General Chemistry
General Biochemistry, Genetics and Molecular Biology
General Physics and Astronomy

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Carter, J. M., Chumsri, S., Hinerfeld, D. A., Ma, Y., Wang, X., Zahrieh, D., Hillman, D. W., Tenner, K. S., Kachergus, J. M., Brauer, H. A., Warren, S. E., Henderson, D., Shi, J., Liu, Y., Joensuu, H., Lindman, H., Leon-Ferre, R. A., Boughey, J. C., Liu, M. C., ... Thompson, E. A. (2023). Distinct spatial immune microlandscapes are independently associated with outcomes in triple-negative breast cancer. Nature communications, 14(1), Article 2215. https://doi.org/10.1038/s41467-023-37806-0

Carter, JM , Chumsri, S, Hinerfeld, DA, Ma, Y, Wang, X, Zahrieh, D, Hillman, DW, Tenner, KS, Kachergus, JM, Brauer, HA, Warren, SE, Henderson, D, Shi, J, Liu, Y, Joensuu, H, Lindman, H, Leon-Ferre, RA, Boughey, JC , Liu, MC, Ingle, JN, Kalari, KR , Couch, FJ , Knutson, KL , Goetz, MP, Perez, EA & Thompson, EA 2023, 'Distinct spatial immune microlandscapes are independently associated with outcomes in triple-negative breast cancer', Nature communications, vol. 14, no. 1, 2215. https://doi.org/10.1038/s41467-023-37806-0

@article{6b15c2e3067140dcb7a1ee31c72eaa8e,

title = "Distinct spatial immune microlandscapes are independently associated with outcomes in triple-negative breast cancer",

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-na{\"i}ve (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-na{\"i}ve 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.",

author = "Carter, {Jodi M.} and Saranya Chumsri and Hinerfeld, {Douglas A.} and Yaohua Ma and Xue Wang and David Zahrieh and Hillman, {David W.} and Tenner, {Kathleen S.} and Kachergus, {Jennifer M.} and Brauer, {Heather Ann} and Warren, {Sarah E.} and David Henderson and Ji Shi and Yi Liu and Heikki Joensuu and Henrik Lindman and Leon-Ferre, {Roberto A.} and Boughey, {Judy C.} and Liu, {Minetta C.} and Ingle, {James N.} and Kalari, {Krishna R.} and Couch, {Fergus J.} and Knutson, {Keith L.} and Goetz, {Matthew P.} and Perez, {Edith A.} and Thompson, {E. Aubrey}",

note = "Publisher Copyright: {\textcopyright} 2023, The Author(s).",

year = "2023",

month = dec,

doi = "10.1038/s41467-023-37806-0",

language = "English (US)",

volume = "14",

journal = "Nature communications",

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T1 - Distinct spatial immune microlandscapes are independently associated with outcomes in triple-negative breast cancer

AU - Carter, Jodi M.

AU - Chumsri, Saranya

AU - Hinerfeld, Douglas A.

AU - Ma, Yaohua

AU - Wang, Xue

AU - Zahrieh, David

AU - Hillman, David W.

AU - Tenner, Kathleen S.

AU - Kachergus, Jennifer M.

AU - Brauer, Heather Ann

AU - Warren, Sarah E.

AU - Henderson, David

AU - Shi, Ji

AU - Liu, Yi

AU - Joensuu, Heikki

AU - Lindman, Henrik

AU - Leon-Ferre, Roberto A.

AU - Boughey, Judy C.

AU - Liu, Minetta C.

AU - Ingle, James N.

AU - Kalari, Krishna R.

AU - Couch, Fergus J.

AU - Knutson, Keith L.

AU - Goetz, Matthew P.

AU - Perez, Edith A.

AU - Thompson, E. Aubrey

PY - 2023/12

Y1 - 2023/12

N2 - 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.

AB - 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.

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JO - Nature communications

JF - Nature communications

IS - 1

M1 - 2215

ER -

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

Abstract

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