A multi-omics analysis of advanced triple-negative breast cancer identifies predictors to chemo-immunotherapy and on-treatment dynamics

@article{renne2026multiomics,
  title = {{A multi-omics analysis of advanced triple-negative breast cancer identifies predictors to chemo-immunotherapy and on-treatment dynamics}},
  author = {Nicolaas Van Renne and Elisa Agostinetto and Andrea Joaquín García and Marie Morfouace and Marcin Możejko and Zoë Denis and Sophie Déglise and Bernd Bodenmiller and Henoch S. Hong and David Venet and Marcela Carausu and Robin Liechti and Stéphanie Tissot and Sylvie Rusakiewicz and Mattia Rediti and Xavier Catteau and Daniel Schulz and Delphine Loirat and Daniel Herrero Saboya and Philippe Aftimos and Matteo Benelli and Angel L. Guerrero-Zotano and Andrea Gombos and Hans Wildiers and Jip Van Dinter and Ariane Sickinghe and Nicolas Penel and Jean-Charles Goeminne and Júlio Oliveira and Birute Brasiuniene and Emanuela Romano and Justin M. Balko and Marleen Kok and Ewa Szczurek and Christos Sotiriou and Laurence Buisseret},
  journal = {Cell Reports Medicine},
  year = {2026},
  month = sep,
  doi = {10.1016/j.xcrm.2026.103080},
  url = {https://doi.org/10.1016/j.xcrm.2026.103080},
  note = {CC BY 4.0},
}

TY  - JOUR
TI  - A multi-omics analysis of advanced triple-negative breast cancer identifies predictors to chemo-immunotherapy and on-treatment dynamics
AU  - Nicolaas Van Renne
AU  - Elisa Agostinetto
AU  - Andrea Joaquín García
AU  - Marie Morfouace
AU  - Marcin Możejko
AU  - Zoë Denis
AU  - Sophie Déglise
AU  - Bernd Bodenmiller
AU  - Henoch S. Hong
AU  - David Venet
AU  - Marcela Carausu
AU  - Robin Liechti
AU  - Stéphanie Tissot
AU  - Sylvie Rusakiewicz
AU  - Mattia Rediti
AU  - Xavier Catteau
AU  - Daniel Schulz
AU  - Delphine Loirat
AU  - Daniel Herrero Saboya
AU  - Philippe Aftimos
AU  - Matteo Benelli
AU  - Angel L. Guerrero-Zotano
AU  - Andrea Gombos
AU  - Hans Wildiers
AU  - Jip Van Dinter
AU  - Ariane Sickinghe
AU  - Nicolas Penel
AU  - Jean-Charles Goeminne
AU  - Júlio Oliveira
AU  - Birute Brasiuniene
AU  - Emanuela Romano
AU  - Justin M. Balko
AU  - Marleen Kok
AU  - Ewa Szczurek
AU  - Christos Sotiriou
AU  - Laurence Buisseret
PY  - 2026
DA  - 2026/09/29
JO  - Cell Reports Medicine
DO  - 10.1016/j.xcrm.2026.103080
UR  - https://doi.org/10.1016/j.xcrm.2026.103080
AB  - No validated biomarkers beyond PD-L1 currently guide immune checkpoint inhibition (ICI) in advanced triple-negative breast cancer (TNBC), and how tumors remodel their microenvironment in response to ICI remains incompletely understood. We perform a temporal analysis of patients with advanced TNBC treated with chemo-immunotherapy in the SYNERGY trial (NCT03616886; n = 84) and the EORTC-1553-SPECTA initiative (NCT02834884; n = 38) using RNA sequencing, whole-exome sequencing, multiplex immunofluorescence, and imaging mass cytometry. A transcriptomic progression-free survival (PFS)-based risk signature stratifies outcomes and is validated across ICI-treated cohorts, while showing context-dependent behavior in non-ICI settings. Favorable outcomes are associated with immune-enriched tumors with organized lymphoid architecture, while poor outcomes are linked to fibrotic, angiogenic microenvironments with frequent PI3K alterations. Upon treatment, early progression was characterized by fibrovascular remodeling, macrophage expansion, and upregulation of alternative immunosuppressive mediators. These findings establish fibrovascular and myeloid reprogramming as a coordinated resistance program, identify actionable therapeutic targets, and support microenvironment stratification in future ICI-based trials.
SN  - 2666-3791
ER  -