Immunosuppressive myeloid cells induce mesenchymal-like breast cancer stem cells by a membrane-bound TGF-β1-dependent mechanism

  • Cell Rep. 2026 Jun 18;45(7):117568. doi: 10.1016/j.celrep.2026.117568.
Thomas Boyer  1 ,  Céline Blaye  2 ,  Domitille Chalopin  3 ,  Mathilde Madéry  1 ,  Jonathan Boucher  4 ,  Alexandra Moisand  1 ,  Audrey Theodoly-Lannes  1 ,  Julie Giraud  5 ,  Florent Peyraud  1 ,  Lornella Seeneevassen  6 ,  Clément Klein  1 ,  Samy Mebroukine  1 ,  Sophie Auriol  7 ,  Assia Chaibi  8 ,  Atika Zouine  9 ,  Julien Izotte  10 ,  Léa Mora Charrot  10 ,  Darya Alizadeh  11 ,  Richard Iggo  6 ,  Gaetan MacGrogan  7 ,  Baptiste Lamarthée  12 ,  Bernard Bonnotte  13 ,  Eric Bonneil  4 ,  Philippe P Roux  14 ,  Christine Varon  6 ,  Charlotte Domblides  15 ,  Nicolas Larmonier  16
Affiliations
  • 1. University of Bordeaux, CNRS, Inserm, ImmunoConcEpT, UMR5164, ERL 1303, 33000 Bordeaux, France.
  • 2. University of Bordeaux, CNRS, Inserm, ImmunoConcEpT, UMR5164, ERL 1303, 33000 Bordeaux, France; Department of Medicine, Institut Bergonié, Bordeaux, France.
  • 3. University of Bordeaux, CNRS, Inserm, ImmunoConcEpT, UMR5164, ERL 1303, 33000 Bordeaux, France; University of Bordeaux, CNRS, IBGC, UMR 5095, 33000 Bordeaux, France.
  • 4. Institut de Recherche en Immunologie et en Cancérologie de l'Université de Montréal, Université de Montréal, Montreal, QC, Canada.
  • 5. University of Bordeaux, CNRS, Inserm, ImmunoConcEpT, UMR5164, ERL 1303, 33000 Bordeaux, France; University of Bordeaux, INSERM, BRIC, U 1312, 33000 Bordeaux, France.
  • 6. University of Bordeaux, INSERM, BRIC, U 1312, 33000 Bordeaux, France.
  • 7. Department of Medicine, Institut Bergonié, Bordeaux, France.
  • 8. Explicyte, Bordeaux, France.
  • 9. University of Bordeaux, CNRS, INSERM, TBM-Core, US5, UAR 3427, 33000 Bordeaux, France.
  • 10. University of Bordeaux, Animalerie A2, Département STS, Service Commun des Animaleries, 33000 Bordeaux, France.
  • 11. City of Hope, T Cell Therapeutics Research Labs, Cellular Immunotherapy Center, Department of Hematology and Hematopoietic Cell Transplantation, Duarte, CA, USA.
  • 12. University Marie et Louis Pasteur, EFS, INSERM, UMR RIGHT, 25000 Besançon, France.
  • 13. University of Bourgogne, INSERM, UMR1098, CHU de Dijon, CHU de Dijon Dijon, France.
  • 14. Institut de Recherche en Immunologie et en Cancérologie de l'Université de Montréal, Université de Montréal, Montreal, QC, Canada; Département de Pathologie et Biologie Cellulaire, Faculté de Médecine, Université de Montréal, Montreal, QC, Canada.
  • 15. University of Bordeaux, CNRS, Inserm, ImmunoConcEpT, UMR5164, ERL 1303, 33000 Bordeaux, France; CHU de Bordeaux, Department of Medical Oncology, Hôpital Saint-André, UMR 5164, 33000 Bordeaux, France.
  • 16. University of Bordeaux, CNRS, Inserm, ImmunoConcEpT, UMR5164, ERL 1303, 33000 Bordeaux, France. Electronic address: [email protected].
PMID: 42319830 DOI: 10.1016/j.celrep.2026.117568
Abstract

Suppressive myeloid cells play a central role in Cancer escape from anti-tumor immunity and exert multiple pro-tumoral activities, including the promotion of Cancer cell survival, invasion, and metastasis. Recent evidence suggests that certain subsets may also influence tumor heterogeneity and cellular plasticity. However, their role in Cancer stem cell promotion and plasticity and the underlying molecular mechanisms have yet to be deciphered. Here we demonstrate that human immunosuppressive myeloid cells, generated in vitro or isolated from patients with breast Cancer, induce Cancer stem-like cells exhibiting mesenchymal features. This cancer-stemness-inducing function was restricted to a CD52-expressing myeloid subset. Single cell transcriptomic- and surface proteome-based interactome analyses identify membrane-bound TGF-β1 as a potential mediator of this effect. Functional inhibition of the TGF-β1 pathway blocks stem-like feature induction by suppressive myeloid cells. These results provide insights into the Cancer stemness-promoting capacity of suppressive myeloid cells and its associated molecular mechanisms in breast Cancer.

Keywords
CP: cancer; CP: immunology; MDSC; anti-tumor immunity; cancer stemness; immunosuppression; membrane-bound TGF-β; mesenchymal CSC; myeloid cells.
Products