Spatial transcriptomics reveals substantial heterogeneity in triple-negative breast cancer with potential clinical implications
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.
Authors
- Frédéric Lifrange
- Ghizlane Rouas
- Andrea Joaquin Garcia (ORCID: https://orcid.org/0000-0002-5847-1310)
- Yuvarani Masarapu (ORCID: https://orcid.org/0000-0002-3267-2085)
- Kim Thrane (ORCID: https://orcid.org/0000-0003-3109-5551)
- Denis Larsimont (ORCID: https://orcid.org/0000-0003-2152-253X)
- Laurence Buisseret (ORCID: https://orcid.org/0000-0002-3751-0819)
- Floriane Dupont
- Linda Kvastad (ORCID: https://orcid.org/0000-0001-5869-3485)
- Françoise Rothé (ORCID: https://orcid.org/0009-0003-2625-5642)
- David Venet (ORCID: https://orcid.org/0000-0001-9038-5271)
- Linnea Stenbeck (ORCID: https://orcid.org/0000-0002-0210-7886)
- Sami Saarenpää (ORCID: https://orcid.org/0000-0003-4731-6857)
- Joakim Lundeberg (ORCID: https://orcid.org/0000-0003-4313-1601)
- Christos Sotiriou (ORCID: https://orcid.org/0000-0002-5745-9977)
- Nayanika Bhalla (ORCID: https://orcid.org/0000-0002-6800-0432)
- Marcela Carausu (ORCID: https://orcid.org/0000-0002-2414-2500)
- Mattia Rediti (ORCID: https://orcid.org/0000-0002-6713-2599)
- Michail Ignatiadis (ORCID: https://orcid.org/0000-0002-4493-3748)
- Eva Gracia Villacampa (ORCID: https://orcid.org/0000-0003-0353-2101)
- Lovisa Franzén (ORCID: https://orcid.org/0000-0003-3755-718X)
- Ligia Craciun (ORCID: https://orcid.org/0000-0001-6540-8232)
- Xiaoxiao Wang (ORCID: https://orcid.org/0000-0002-3996-7900)
Institutions
- Université Libre de Bruxelles (BE)
- Institut Jules Bordet (BE)
- KTH Royal Institute of Technology (SE)
Publication Details
- Journal
- Nature Communications
- Published
- 2024-11-26
- DOI
- https://doi.org/10.1038/s41467-024-54145-w
- Citations
- 49
- Primary Topic
- Single-cell and spatial transcriptomics
- Type
- article
- Field-Weighted Citation Impact
- 11.46
Funders
- Breast Cancer Research Foundation
- Fonds De La Recherche Scientifique - FNRS
- Cancerfonden
- Fondation Rose et Jean Hoguet