[en] While triple-negative breast cancer (TNBC) is known to be heterogeneous at the genomic and transcriptomic levels, spatial information on tumor organization and cell composition is still lacking. Here, we investigate TNBC tumor architecture including its microenvironment using spatial transcriptomics on a series of 92 patients. We perform an in-depth characterization of tumor and stroma organization and composition using an integrative approach combining histomorphological and spatial transcriptomics. Furthermore, a detailed molecular characterization of tertiary lymphoid structures leads to identify a gene signature strongly associated to disease outcome and response to immunotherapy in several tumor types beyond TNBC. A stepwise clustering analysis identifies nine TNBC spatial archetypes, further validated in external datasets. Several spatial archetypes are associated with disease outcome and characterized by potentially actionable features. In this work, we provide a comprehensive insight into the complexity of TNBC ecosystem with potential clinical relevance, opening avenues for treatment tailoring including immunotherapy.
Disciplines :
Oncology
Author, co-author :
Wang, Xiaoxiao ; Breast Cancer Translational Research Laboratory J-C Heuson, Institut Jules Bordet, Université Libre de Bruxelles, Hôpital Universitaire de Bruxelles, Brussels, Belgium ; Medical Oncology Department, Institut Jules Bordet, Université Libre de Bruxelles, Hôpital Universitaire de Bruxelles, Brussels, Belgium
Venet, David; Breast Cancer Translational Research Laboratory J-C Heuson, Institut Jules Bordet, Université Libre de Bruxelles, Hôpital Universitaire de Bruxelles, Brussels, Belgium
Lifrange, Frédéric ; Department of Pathology, University Hospital Center of Liège, Liège, Belgium
Larsimont, Denis; Department of Pathology, Institut Jules Bordet, Université Libre de Bruxelles, Hôpital Universitaire de Bruxelles, Brussels, Belgium
Rediti, Mattia ; Breast Cancer Translational Research Laboratory J-C Heuson, Institut Jules Bordet, Université Libre de Bruxelles, Hôpital Universitaire de Bruxelles, Brussels, Belgium
Stenbeck, Linnea; Department of Gene Technology, KTH Royal Institute of Technology, Stockholm, Sweden
Dupont, Floriane; Breast Cancer Translational Research Laboratory J-C Heuson, Institut Jules Bordet, Université Libre de Bruxelles, Hôpital Universitaire de Bruxelles, Brussels, Belgium
Rouas, Ghizlane; Breast Cancer Translational Research Laboratory J-C Heuson, Institut Jules Bordet, Université Libre de Bruxelles, Hôpital Universitaire de Bruxelles, Brussels, Belgium
Garcia, Andrea Joaquin; Breast Cancer Translational Research Laboratory J-C Heuson, Institut Jules Bordet, Université Libre de Bruxelles, Hôpital Universitaire de Bruxelles, Brussels, Belgium
Craciun, Ligia; Department of Pathology, Institut Jules Bordet, Université Libre de Bruxelles, Hôpital Universitaire de Bruxelles, Brussels, Belgium
Buisseret, Laurence; Breast Cancer Translational Research Laboratory J-C Heuson, Institut Jules Bordet, Université Libre de Bruxelles, Hôpital Universitaire de Bruxelles, Brussels, Belgium ; Medical Oncology Department, Institut Jules Bordet, Université Libre de Bruxelles, Hôpital Universitaire de Bruxelles, Brussels, Belgium
Ignatiadis, Michail ; Breast Cancer Translational Research Laboratory J-C Heuson, Institut Jules Bordet, Université Libre de Bruxelles, Hôpital Universitaire de Bruxelles, Brussels, Belgium ; Medical Oncology Department, Institut Jules Bordet, Université Libre de Bruxelles, Hôpital Universitaire de Bruxelles, Brussels, Belgium
Carausu, Marcela; Breast Cancer Translational Research Laboratory J-C Heuson, Institut Jules Bordet, Université Libre de Bruxelles, Hôpital Universitaire de Bruxelles, Brussels, Belgium
Bhalla, Nayanika ; Department of Gene Technology, KTH Royal Institute of Technology, Stockholm, Sweden
Masarapu, Yuvarani ; Department of Gene Technology, KTH Royal Institute of Technology, Stockholm, Sweden
Villacampa, Eva Gracia ; Department of Gene Technology, KTH Royal Institute of Technology, Stockholm, Sweden
Franzén, Lovisa ; Department of Gene Technology, KTH Royal Institute of Technology, Stockholm, Sweden
Saarenpää, Sami ; Department of Gene Technology, KTH Royal Institute of Technology, Stockholm, Sweden
Kvastad, Linda ; Department of Gene Technology, KTH Royal Institute of Technology, Stockholm, Sweden
Thrane, Kim; Department of Gene Technology, KTH Royal Institute of Technology, Stockholm, Sweden
Lundeberg, Joakim ; Department of Gene Technology, KTH Royal Institute of Technology, Stockholm, Sweden
Rothé, Françoise; Breast Cancer Translational Research Laboratory J-C Heuson, Institut Jules Bordet, Université Libre de Bruxelles, Hôpital Universitaire de Bruxelles, Brussels, Belgium
Sotiriou, Christos ; Breast Cancer Translational Research Laboratory J-C Heuson, Institut Jules Bordet, Université Libre de Bruxelles, Hôpital Universitaire de Bruxelles, Brussels, Belgium. christos.sotiriou@hubruxelles.be ; Medical Oncology Department, Institut Jules Bordet, Université Libre de Bruxelles, Hôpital Universitaire de Bruxelles, Brussels, Belgium. christos.sotiriou@hubruxelles.be
BCRF - Breast Cancer Research Foundation F.R.S.-FNRS - Fonds de la Recherche Scientifique Cancerfonden
Funding text :
This research was supported by the Fondation Julie-Fran\u00E7oise Drion, the\u00A0Fondation contre le cancer, the Breast Cancer Research Foundation, the Association Jules Bordet, and the Belgian Fonds National de la Recherche Scientifique (F.R.S.-FNRS). X.W. was supported by the Belgian Fonds National de la Recherche Scientifique (F.R.S.-FNRS). D.V. was supported by the Foundation Julie-Fran\u00E7oise Drion.\u00A0M.R. was supported by T\u00E9l\u00E9vie and the Belgian Fonds National de la Recherche Scientifique (F.R.S.-FNRS). M.R. was supported by T\u00E9l\u00E9vie and the Belgian Fonds National de la Recherche Scientifique (F.R.S.-FNRS), and by Fondation Rose et Jean Hoguet. J.L. was supported by the Swedish Cancer Society. Computational resources have been provided by the Consortium des \u00C9quipements de Calcul Intensif (C\u00C9CI), funded by the Fonds de la Recherche Scientifique de Belgique (F.R.S.-FNRS) under Grant No. 2.5020.11 and by the Walloon Region. We acknowledge Maja Marklund, Konstantin Carlberg, Ludvig Larsson and Annelie Mollbrink for their involvement in the experimental STs workflow, David Gacquer for his contribution to the conceptualization of the figures and Samira Majjaj for the bulk RNA extraction and library preparation.This research was supported by the Fondation Julie-Fran\u00E7oise Drion, the Fondation contre le cancer, the Breast Cancer Research Foundation, the Association Jules Bordet, and the Belgian Fonds National de la Recherche Scientifique (F.R.S.-FNRS). X.W. was supported by the Belgian Fonds National de la Recherche Scientifique (F.R.S.-FNRS). D.V. was supported by the Foundation Julie-Fran\u00E7oise Drion. M.R. was supported by T\u00E9l\u00E9vie and the Belgian Fonds National de la Recherche Scientifique (F.R.S.-FNRS). M.R. was supported by T\u00E9l\u00E9vie and the Belgian Fonds National de la Recherche Scientifique (F.R.S.-FNRS), and by Fondation Rose et Jean Hoguet. J.L. was supported by the Swedish Cancer Society. Computational resources have been provided by the Consortium des \u00C9quipements de Calcul Intensif (C\u00C9CI), funded by the Fonds de la Recherche Scientifique de Belgique (F.R.S.-FNRS) under Grant No. 2.5020.11 and by the Walloon Region. We acknowledge Maja Marklund, Konstantin Carlberg, Ludvig Larsson and Annelie Mollbrink for their involvement in the experimental STs workflow, David Gacquer for his contribution to the conceptualization of the figures and Samira Majjaj for the bulk RNA extraction and library preparation.
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