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

Author

Listed:
  • Xiaoxiao Wang

    (Hôpital Universitaire de Bruxelles
    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
    Hôpital Universitaire de Bruxelles)

  • Michail Ignatiadis

    (Hôpital Universitaire de Bruxelles
    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
    Hôpital Universitaire de Bruxelles)

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.

Suggested Citation

  • Xiaoxiao Wang & David Venet & Frédéric Lifrange & Denis Larsimont & Mattia Rediti & Linnea Stenbeck & Floriane Dupont & Ghizlane Rouas & Andrea Joaquin Garcia & Ligia Craciun & Laurence Buisseret & Mi, 2024. "Spatial transcriptomics reveals substantial heterogeneity in triple-negative breast cancer with potential clinical implications," Nature Communications, Nature, vol. 15(1), pages 1-22, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-54145-w
    DOI: 10.1038/s41467-024-54145-w
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    as
    1. Alma Andersson & Ludvig Larsson & Linnea Stenbeck & Fredrik Salmén & Anna Ehinger & Sunny Z. Wu & Ghamdan Al-Eryani & Daniel Roden & Alex Swarbrick & Åke Borg & Jonas Frisén & Camilla Engblom & Joakim, 2021. "Spatial deconvolution of HER2-positive breast cancer delineates tumor-associated cell type interactions," Nature Communications, Nature, vol. 12(1), pages 1-14, December.
    2. Rita Cabrita & Martin Lauss & Adriana Sanna & Marco Donia & Mathilde Skaarup Larsen & Shamik Mitra & Iva Johansson & Bengt Phung & Katja Harbst & Johan Vallon-Christersson & Alison Schoiack & Kristina, 2020. "Author Correction: Tertiary lymphoid structures improve immunotherapy and survival in melanoma," Nature, Nature, vol. 580(7801), pages 1-1, April.
    3. Soizic Garaud & Marie-Caroline Dieu-Nosjean & Karen Willard-Gallo, 2022. "T follicular helper and B cell crosstalk in tertiary lymphoid structures and cancer immunotherapy," Nature Communications, Nature, vol. 13(1), pages 1-4, December.
    4. Xiao Qian Wang & Esther Danenberg & Chiun-Sheng Huang & Daniel Egle & Maurizio Callari & Begoña Bermejo & Matteo Dugo & Claudio Zamagni & Marc Thill & Anton Anton & Stefania Zambelli & Stefania Russo , 2023. "Spatial predictors of immunotherapy response in triple-negative breast cancer," Nature, Nature, vol. 621(7980), pages 868-876, September.
    5. Rita Cabrita & Martin Lauss & Adriana Sanna & Marco Donia & Mathilde Skaarup Larsen & Shamik Mitra & Iva Johansson & Bengt Phung & Katja Harbst & Johan Vallon-Christersson & Alison Schoiack & Kristina, 2020. "Tertiary lymphoid structures improve immunotherapy and survival in melanoma," Nature, Nature, vol. 577(7791), pages 561-565, January.
    6. Anjali Rao & Dalia Barkley & Gustavo S. França & Itai Yanai, 2021. "Exploring tissue architecture using spatial transcriptomics," Nature, Nature, vol. 596(7871), pages 211-220, August.
    7. Beth A. Helmink & Sangeetha M. Reddy & Jianjun Gao & Shaojun Zhang & Rafet Basar & Rohit Thakur & Keren Yizhak & Moshe Sade-Feldman & Jorge Blando & Guangchun Han & Vancheswaran Gopalakrishnan & Yuanx, 2020. "B cells and tertiary lymphoid structures promote immunotherapy response," Nature, Nature, vol. 577(7791), pages 549-555, January.
    8. Dora Hammerl & John W. M. Martens & Mieke Timmermans & Marcel Smid & Anita M. Trapman-Jansen & Renée Foekens & Olga I. Isaeva & Leonie Voorwerk & Hayri E. Balcioglu & Rebecca Wijers & Iris Nederlof & , 2021. "Spatial immunophenotypes predict response to anti-PD1 treatment and capture distinct paths of T cell evasion in triple negative breast cancer," Nature Communications, Nature, vol. 12(1), pages 1-13, December.
    9. Oscar M. Rueda & Stephen-John Sammut & Jose A. Seoane & Suet-Feung Chin & Jennifer L. Caswell-Jin & Maurizio Callari & Rajbir Batra & Bernard Pereira & Alejandra Bruna & H. Raza Ali & Elena Provenzano, 2019. "Dynamics of breast-cancer relapse reveal late-recurring ER-positive genomic subgroups," Nature, Nature, vol. 567(7748), pages 399-404, March.
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