Soft matrix promotes immunosuppression in tumor-resident immune cells via COX-FGF2 signaling

Aino Peura, Rita Turpin, Ruixian Liu, Maria Heilala, Maria Salmela, July Aung, Piia Mikkonen, Minna Mutka, Panu E. Kovanen, Laura Niinikoski, Tuomo Meretoja, Johanna Mattson, Päivi Heikkilä, Päivi Palanne, Tiina Kantanen, Mikko Kilpeläinen, Outi Ukkonen, Maija Hollmén, Topi A. Tervonen, Juha Klefström () and Pauliina M. Munne ()
Additional contact information
Aino Peura: University of Helsinki
Rita Turpin: University of Helsinki
Ruixian Liu: University of Helsinki
Maria Heilala: Aalto University
Maria Salmela: University of Helsinki and Biocenter Finland
July Aung: University of Helsinki
Piia Mikkonen: UPM-Kymmene Corporation
Minna Mutka: Helsinki University Central Hospital and University of Helsinki
Panu E. Kovanen: Helsinki University Central Hospital and University of Helsinki
Laura Niinikoski: Helsinki University Hospital and University of Helsinki
Tuomo Meretoja: Helsinki University Hospital and University of Helsinki
Johanna Mattson: University of Helsinki & Helsinki University Hospital
Päivi Heikkilä: Helsinki University Central Hospital and University of Helsinki
Päivi Palanne: KYMSOTE
Tiina Kantanen: Helsinki University Central Hospital and University of Helsinki
Mikko Kilpeläinen: KYMSOTE
Outi Ukkonen: KYMSOTE
Maija Hollmén: Tykistökatu 6A
Topi A. Tervonen: University of Helsinki
Juha Klefström: University of Helsinki
Pauliina M. Munne: University of Helsinki

Nature Communications, 2025, vol. 16, issue 1, 1-17

Abstract: Abstract Mechanical forces of the tumor microenvironment change dynamically during key events of tumorigenesis such as invasion and metastasis. These changes in compressive forces often affect the breast cancer cell phenotype. However, it is lesser known how these dynamic mechanical forces in the tumor microenvironment affect the phenotypes of tumor infiltrated leukocytes (TIL) and their subsequent anticancer activities. Here we find, in primary patient-derived explant cultures (PDEC) containing resident TILs, that low compression promotes a change in the original identity of breast cancer cells from luminal to a more mesenchymal and undifferentiated state. These altered tumor cells induce an upregulation of immunosuppressive cytokines such as interleukin-10 (IL-10) and Transforming Growth Factor Beta (TGF-β), as well as polarization of macrophages towards pro-tumor M2(Gc)-type and depletion of CD8+ effector memory T-cells. These immunosuppressive events are mediated by tumor cell derived fibroblast growth factor 2 (FGF2) and prostaglandin E2 (PGE2). We also find that FGF2 rich areas in primary tumors show enrichment in M2-like-macrophages and diminished numbers of CD8 + T and B-cells. Our results suggest that low compressive forces in the tumor microenvironment induce local immunosuppression via FGF2 secretion arising from phenotypic plasticity of tumor cells.

Date: 2025
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-025-60092-x Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-60092-x

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-025-60092-x

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().