Compartment-specific tumor-infiltrating immune cells and prognosis in breast cancer

Breast cancer immune response is important to patient outcome, but the prognostic interaction between tissue-infiltrating immune cell (TIIC) types is not well-characterized. We evaluated the associations between CD8<sup>+</sup>, FOXP3+, CD20<sup>+</sup>, and CD163<sup>+</sup> TIICs and breast cancer-specific survival (BCSS). We developed an AI in Halo to score TIIC percentage by compartment (overall, stromal, or intra-tumoral) in 99,051 microarray images from 12,285 female breast cancers. The associations between log-transformed TIIC scores and BCSS were assessed using Cox regression. CD8<sup>+</sup> and FOXP3+ TIICs were associated with better BCSS in ER-negative disease; CD8<sup>+</sup> and CD20<sup>+</sup> TIICs were associated with a better prognosis in ER-positive disease; and CD163<sup>+</sup> TIICs were associated with a poorer prognosis in ER-positive disease in multi-marker models. These results may have implications for breast cancer immunotherapy.

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Publication Details

Journal
iScience
Published
2026-01-21
DOI
https://doi.org/10.1016/j.isci.2026.114759
Primary Topic
Cancer Immunotherapy and Biomarkers
Type
article
Field-Weighted Citation Impact
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article

Compartment-specific tumor-infiltrating immune cells and prognosis in breast cancer

Thomas Choudary Putti, Scott M. Lawrence, Alpa V. Patel, Melissa H. Cessna et al.
iScience
Cancer Immunotherapy and Biomarkers
article

Compartment-specific tumor-infiltrating immune cells and prognosis in breast cancer

Thomas Choudary Putti, Scott M. Lawrence, Alpa V. Patel, Melissa H. Cessna, Karun Mutreja, Amy Berrington de González, Máire A. Duggan, Alexandra J. van den Broek, Sabine Behrens, John W.M. Martens, Jodi L. Miller, Rob B. van der Luijt, J. Gronwald, LI Jing-mei, Ute Hamann, Doug F. Easton, Annette Heemskerk-Gerritsen, Nicki J Camp, Nadia Obi, Aaron J. Bernstein, Mikael Hartman, Katarzyna Bialkowska, Rudolf Kaaks, Federico Canzian, Tabea Maurer DiplPsych, Maartje Hooning, Pietro Liò, Clara Bodelon, H.Raza Ali, Hugo Horlings, Hermann Brenner, Anna Marie Mulligan, Jolanta Lissowska, Irene Andrulis, Will Tapper, Renske Keeman, Peter Devilee, Stephen Chanock, Jan Lubiński, J.Louise Jones, Fiona M. Blows, Diana Eccles, Agnes Jager, Antoinette Hollestelle, Mustapha Abubakar, Ania Jakubowska, Marjanka K. Schmidt, Jenny Chang-Claude, Roger L. Milne, Paul D.P. Pharoah, Simon S. Cross, Fergus J. Couch, Gord Glendon, Montse Garcia-Closas, Muhammad Rashid, Siddhartha Yadav, Ben Schöttker, James M. Hodge, Angela Cox, Wilma Mesker, Thomas Ahearn
article en

Abstract

Breast cancer immune response is important to patient outcome, but the prognostic interaction between tissue-infiltrating immune cell (TIIC) types is not well-characterized. We evaluated the associations between CD8<sup>+</sup>, FOXP3+, CD20<sup>+</sup>, and CD163<sup>+</sup> TIICs and breast cancer-specific survival (BCSS). We developed an AI in Halo to score TIIC percentage by compartment (overall, stromal, or intra-tumoral) in 99,051 microarray images from 12,285 female breast cancers. The associations between log-transformed TIIC scores and BCSS were assessed using Cox regression. CD8<sup>+</sup> and FOXP3+ TIICs were associated with better BCSS in ER-negative disease; CD8<sup>+</sup> and CD20<sup>+</sup> TIICs were associated with a better prognosis in ER-positive disease; and CD163<sup>+</sup> TIICs were associated with a poorer prognosis in ER-positive disease in multi-marker models. These results may have implications for breast cancer immunotherapy.

iScienceVol. 29(2)
Intermountain Healthcare (US), Agency for Science, Technology and Research (SG), Cedars-Sinai Medical Center (US), American Cancer Society (US), National Institutes of Health (US), University Health Network (CA), Institute of Cancer Research (GB), Universität Hamburg (DE), The University of Melbourne (AU), National University of Singapore (SG), Queen Mary University of London (GB), University of Calgary (CA), German Cancer Research Center (DE), University of Toronto (CA), Cancer Council Victoria (AU), Hebrew University of Jerusalem (IL), Lunenfeld-Tanenbaum Research Institute (CA), University of Utah (US), Heidelberg University (DE), University of Cambridge (GB), Leiden University Medical Center (NL), Huntsman Cancer Institute (US), Cancer Research UK (GB), The Netherlands Cancer Institute (NL), Office of the Director (US), University Medical Center Hamburg-Eppendorf (DE), Oncode Institute (NL), Monash Health (AU), Mayo Clinic in Arizona (US), Frederick National Laboratory for Cancer Research (US), Sinai Health System (CA), Centrum Onkologii (PL), National Cancer Institute (US), National Center for Advancing Translational Sciences (US), Erasmus MC Cancer Institute (NL), National University Health System (SG), University of Southampton (GB), Division of Cancer Epidemiology and Genetics, Monash University (AU), Pomeranian Medical University (PL), University of Sheffield (GB)
U.S. Department of Health and Human Services, Cancer Research UK, National Institute for Health and Care Research, Department of Health and Social Care, European Commission, National Institutes of Health, Centers for Disease Control and Prevention, NIHR Cambridge Biomedical Research Centre, Cancer Research UK Cambridge Institute, University of Cambridge, National Cancer Institute
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