Spatial transcriptomics reveals substantial heterogeneity in triple-negative breast cancer with potential clinical implications

Xiaoxiao Wang, David Venet, Frédéric Lifrange, Denis Larsimont, Mattia Rediti, Linnea Stenbeck, Floriane Dupont, Ghizlane Rouas, Andrea Joaquin Garcia, Ligia Craciun, Laurence Buisseret, Michail Ignatiadis, Marcela Carausu, Nayanika Bhalla, Yuvarani Masarapu, Eva Gracia Villacampa, Lovisa Franzén, Sami Saarenpää, Linda Kvastad, Kim Thrane, Joakim Lundeberg, Françoise Rothé and Christos Sotiriou ()
Additional contact information
Xiaoxiao Wang: Hôpital Universitaire de Bruxelles
David Venet: Hôpital Universitaire de Bruxelles
Frédéric Lifrange: University Hospital Center of Liège
Denis Larsimont: Hôpital Universitaire de Bruxelles
Mattia Rediti: Hôpital Universitaire de Bruxelles
Linnea Stenbeck: KTH Royal Institute of Technology
Floriane Dupont: Hôpital Universitaire de Bruxelles
Ghizlane Rouas: Hôpital Universitaire de Bruxelles
Andrea Joaquin Garcia: Hôpital Universitaire de Bruxelles
Ligia Craciun: Hôpital Universitaire de Bruxelles
Laurence Buisseret: Hôpital Universitaire de Bruxelles
Michail Ignatiadis: Hôpital Universitaire de Bruxelles
Marcela Carausu: Hôpital Universitaire de Bruxelles
Nayanika Bhalla: KTH Royal Institute of Technology
Yuvarani Masarapu: KTH Royal Institute of Technology
Eva Gracia Villacampa: KTH Royal Institute of Technology
Lovisa Franzén: KTH Royal Institute of Technology
Sami Saarenpää: KTH Royal Institute of Technology
Linda Kvastad: KTH Royal Institute of Technology
Kim Thrane: KTH Royal Institute of Technology
Joakim Lundeberg: KTH Royal Institute of Technology
Françoise Rothé: Hôpital Universitaire de Bruxelles
Christos Sotiriou: Hôpital Universitaire de Bruxelles

Nature Communications, 2024, vol. 15, issue 1, 1-22

Abstract: Abstract 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.

Date: 2024
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DOI: 10.1038/s41467-024-54145-w

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