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Van Renne, N.* ; Agostinetto, E.* ; Joaquín García, A.* ; Morfouace, M.* ; Możejko, M.* ; Denis, Z.* ; Déglise, S.* ; Bodenmiller, B.* ; Hong, H.S.* ; Venet, D.* ; Carausu, M.* ; Liechti, R.* ; Tissot, S.* ; Rusakiewicz, S.* ; Rediti, M.* ; Catteau, X.* ; Schulz, D.* ; Loirat, D.* ; Herrero Saboya, D.* ; Aftimos, P.* ; Benelli, M.* ; Guerrero-Zotano, A.L.* ; Gombos, A.* ; Wildiers, H.* ; Van Dinter, J.* ; Sickinghe, A.* ; Penel, N.* ; Goeminne, J.C.* ; Oliveira, J.* ; Brasiuniene, B.* ; Romano, E.* ; Balko, J.M.* ; Kok, M.* ; Szczurek, E. ; Sotiriou, C.* ; Buisseret, L.*

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

Cell Rep. Med. 7:103080 (2026)
Verlagsversion Forschungsdaten DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
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.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Biomarkers ; Breast Cancer ; Cancer Immunotherapy ; Immune Checkpoint Inhibitors ; Multi-omics ; Tnbc ; Tumor Microenvironment
ISSN (print) / ISBN 2666-3791
e-ISSN 2666-3791
Zeitschrift Cell Reports Medicine
Quellenangaben Band: 7, Heft: 10, Seiten: , Artikelnummer: 103080 Supplement: ,
Verlag Elsevier
Begutachtungsstatus Peer reviewed
Institut(e) Institute of AI for Health (AIH)