Machine learning-based spatial characterization of tumor-immune microenvironment in the EORTC 10994/BIG 1-00 early breast cancer trial
Breast cancer (BC) represents a heterogeneous ecosystem and elucidation of tumor microenvironment components remains essential. Our study aimed to depict the composition and prognostic correlates of immune infiltrate in early BC, at a multiplex and spatial resolution. Pretreatment tumor biopsies from patients enrolled in the EORTC 10994/BIG 1-00 randomized phase III neoadjuvant trial (NCT00017095) were used; the CNN11 classifier for H&E-based digital TILs (dTILs) quantification and multiplex immunofluorescence were applied, coupled with machine learning (ML)-based spatial features. dTILs were higher in the triple-negative (TN) subtype, and associated with pathological complete response (pCR) in the whole cohort. Total CD4+ and intra-tumoral CD8+ T-cells expression was associated with pCR. Higher immune-tumor cell colocalization was observed in TN tumors of patients achieving pCR. Immune cell subsets were enriched in TP53-mutated tumors. Our results indicate the feasibility of ML-based algorithms for immune infiltrate characterization and the prognostic implications of its abundance and tumor-host interactions.
Authors
- Caroline Boman (ORCID: https://orcid.org/0000-0003-1663-6129)
- Coralie Poncet (ORCID: https://orcid.org/0000-0002-8635-9350)
- David Cameron (ORCID: https://orcid.org/0000-0002-2717-7979)
- Balázs Ács (ORCID: https://orcid.org/0000-0002-0972-4633)
- Georgios C. Manikis (ORCID: https://orcid.org/0000-0002-3396-0644)
- David L. Rimm (ORCID: https://orcid.org/0000-0001-5820-4397)
- Ceren Boyacı (ORCID: https://orcid.org/0000-0001-5598-0243)
- Gaëtan MacGrogan
- Alexios Matikas (ORCID: https://orcid.org/0000-0002-4122-9624)
- Artur Mezheyeuski (ORCID: https://orcid.org/0000-0002-4394-2634)
- Hervé Bonnefoi (ORCID: https://orcid.org/0000-0003-4293-9748)
- Theodoros Foukakis (ORCID: https://orcid.org/0000-0001-8952-9987)
- Michail Ignatiadis (ORCID: https://orcid.org/0000-0002-4493-3748)
- Jonas Bergh (ORCID: https://orcid.org/0000-0001-5526-1847)
- Hemming Johansson (ORCID: https://orcid.org/0000-0002-7156-1468)
- Ioannis Zerdes (ORCID: https://orcid.org/0000-0002-8304-2462)
- Yalai Bai (ORCID: https://orcid.org/0000-0003-4636-0143)
Institutions
- Uppsala University (SE)
- Université Libre de Bruxelles (BE)
- Karolinska University Hospital (SE)
- Université de Bordeaux (FR)
- Inserm (FR)
- Institut Jules Bordet (BE)
- Edinburgh Cancer Research (GB)
- Yale Cancer Center (US)
- Karolinska Institutet (SE)
- Yale University (US)
- European Organisation for Research and Treatment of Cancer (BE)
- Institut Bergonié (FR)
- Vall d'Hebron Institute of Oncology (ES)
- BoRdeaux Institute of onCology (FR)
- Foundation for Research and Technology Hellas (GR)
Publication Details
- Journal
- npj Breast Cancer
- Published
- 2025-03-07
- DOI
- https://doi.org/10.1038/s41523-025-00730-1
- Citations
- 5
- Primary Topic
- Cancer Immunotherapy and Biomarkers
- Type
- article
- Field-Weighted Citation Impact
- 5.23
Funders
- Percy Falks Stiftelse för Forskning Beträffande Prostata- och Bröstcancer
- Cancerfonden
- Vetenskapsrådet
- Radiumhemmets Forskningsfonder