SCS macrophages suppress melanoma by restricting tumor-derived vesicle–B cell interactions
Menée à l'aide de modèles murins, cette étude met en évidence des mécanismes par lesquels des macrophages CD169+ exercent une fonction de suppresseur de tumeurs dans les mélanomes
Tumor-derived extracellular vesicles (tEVs) are important signals in tumor-host cell communication. Yet, how endogenously produced tEVs impact the host in different areas of the body remains unclear. Here we combine imaging and genetic analysis to track melanoma-derived vesicles at organismal, cellular and molecular scales to show that endogenous tEVs efficiently disseminate via lymphatics and preferentially bind subcapsular sinus (SCS) CD169+ macrophages in tumor-draining lymph nodes (tdLNs) in mice and humans. The CD169+ macrophage layer physically blocks tEV dissemination but is undermined during tumor progression and by therapeutic agents. A disrupted SCS macrophage barrier enables tEVs to enter the LN cortex, interact with B cells and foster tumor-promoting humoral immunity. Thus, CD169+ macrophages may act as tumor suppressors by containing tEV spread and ensuing cancer-enhancing immunity.