Publication: JUN Specifies the Local Differentiation and Maintenance of Pro-tumoral Monocyte-Derived Macrophages.

Publié dans: Cancer Res 2026 May; ():

Auteurs: Delfini M, Baudoin E, Guo G, Francois M, Bebien M, Murgaski A, Bettacchioli E, Buferne M, Rastoin O, Belabed D, Moussard P, Mariot C, Baranska A, Verthuy C, Ruffinatto L, Mossadegh-Keller N, Vu Manh TP, Masse M, Soni A, Sieweke MH, Strauss LM, Pauladóttir Jensen M, Doktor TK, Etzerodt A, Auphan-Anezin N, Lawrence T

Résumé

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.

Lien vers Pubmed [PMID] – 42212681

Lien vers le DOI – 10.1158/0008-5472.CAN-25-3974