Myeloid cell development and function : current research
This research team belongs to the UMR 1015 - Tumor immunology and immunotherapies
The research team focuses on understanding the role of macrophages in tumors, particularly how their diversity and function influence cancer progression. Their goal is to discover new therapeutic targets to improve the effectiveness of treatments, including immunotherapies, thus offering better chances of recovery, especially for patients who do not respond to current therapies.
Tumors are complex ecosystems where tumor cells, stromal populations, and various immune cells coexist, including tumor-associated macrophages (TAMs). These macrophages play a crucial role in the tumor microenvironment (TME), promoting pro-tumoral processes such as chronic inflammation, angiogenesis, and suppression of anti-tumor immune responses. Although immunotherapies targeting checkpoint inhibitors, such as PD-1, have shown promising clinical results, their efficacy remains limited to a fraction of patients. TAMs, expressing both PD-L1 and PD-1, are targeted in current therapies, but clinical outcomes are still insufficient to fully validate their therapeutic role.
One major reason for this potential failure lies in the heterogeneity of TAMs, which originate from different ontogenetic sources (embryonic or monocytic) and exhibit functional profiles that vary depending on the duration of their presence in the tumor tissue. Long-established TAMs, in prolonged contact with the tumor, may adopt a phenotype distinct from recently recruited macrophages. These differences are influenced by local factors in the TME, which shape their transcriptional and epigenetic signatures.
Our research project aims to explore this myeloid diversity in cancer by combining specific transgenic murine models that track TAM dynamics based on their ontogeny and duration of residence within the tumor. This approach will be paired with in-depth mapping of TAMs in human cohorts, integrating transcriptomic, proteomic, and epigenetic data to identify new therapeutic targets. Additionally, the use of 3D tumor organoid models and macrophages derived from induced pluripotent stem cells (iPSCs) will help further understand the role of TAMs in pediatric cancers and test targeted therapeutic strategies.
