JUN Specifies the Local Differentiation and Maintenance of Pro-tumoral Monocyte-Derived Macrophages
Tumor-associated macrophages (TAMs) play important roles in cancer progression and resistance to therapy. Recent studies have shown that TAMs include both long-lived resident tissue macrophages (RTMs) and short-lived monocyte-derived macrophages (MDMs) with limited proliferative potential. RTMs and MDMs have been suggested to play divergent roles in tumorigenesis; RTMs are aligned with trophic functions, whereas MDMs are enriched for immune-regulatory pathways. Here we established a specific role for the AP-1 factor JUN in the differentiation and maintenance of MDMs and the specification of pro-tumoral trophic functions during tumor development. Alternatively, the immune-regulatory functions of TAMs remained JUN-independent. JUN was required for the specification and maintenance of pro-tumoral TAMs that support blood vessel maturation and tumor growth. Single-cell transcriptomics analysis uncovered the alternative fates for tumor-infiltrating monocytes and the development of distinct TAM states associated with trophic functions and immune-regulation. These studies demonstrate an important role for JUN in the specification of pro-tumoral monocyte-derived TAMs that could offer opportunities for selective TAM-targeted therapies for cancer.
Authors
- Camille Mariot
- Nathalie Auphan‐Anezin (ORCID: https://orcid.org/0000-0002-1967-5206)
- Toby Lawrence (ORCID: https://orcid.org/0000-0003-0967-6122)
- Marjorie François
- Michael H. Sieweke (ORCID: https://orcid.org/0000-0002-3228-9537)
- Christophe Verthuy
- Anders Etzerodt (ORCID: https://orcid.org/0000-0002-6757-2068)
- Anna Barańska (ORCID: https://orcid.org/0000-0003-4140-1233)
- Éléonore Bettacchioli (ORCID: https://orcid.org/0009-0002-0797-8098)
- Magali Bébien
- Aleksandar Murgaski (ORCID: https://orcid.org/0000-0002-5606-2230)
- Marcello Delfini (ORCID: https://orcid.org/0000-0003-0342-5445)
- Michel Buferne
- Elodie Baudoin
- Olivia Rastoin
- Maria Pauladòttir Jensen (ORCID: https://orcid.org/0009-0002-8624-450X)
- Guo Guo (ORCID: https://orcid.org/0000-0003-1657-9638)
- Marion Massé
- Lucas Ruffinatto
- Noushin Mossadegh-Keller
- Abhinav Soni
- Thomas Koed. Doktor (ORCID: https://orcid.org/0000-0002-5315-8325)
- Thien-Phong Vu Manh (ORCID: https://orcid.org/0000-0002-0294-342X)
- Line Moesgaard. Strauss (ORCID: https://orcid.org/0009-0009-7301-1230)
- Djhienne Belabed (ORCID: https://orcid.org/0009-0009-7302-5237)
- Pauline Moussard (ORCID: https://orcid.org/0009-0004-1267-4261)
Institutions
- University of Southern Denmark (DK)
- King's College London (GB)
- Aarhus University (DK)
- Aix-Marseille Université (FR)
- Aarhus University Hospital (DK)
- VIB-KU Leuven Center for Cancer Biology (BE)
- King's College School (GB)
- Technische Universität Dresden (DE)
Publication Details
- Journal
- Cancer Research
- Published
- 2026-05-29
- DOI
- https://doi.org/10.1158/0008-5472.can-25-3974
- Primary Topic
- Immune cells in cancer
- Type
- article
- Field-Weighted Citation Impact
- 0.00