Stephanie Hugues
"Lymphatic vessels as immunomodulators in Cancer"
Lecture
In melanoma, lymphangiogenesis correlates with metastasis and poor prognosis and promotes immunosuppression. However, it also potentiates immunotherapy by supporting trafficking of immune cells. Lymphatic endothelial cells (LECs) are highly plastic cells that shape their phenotype according to distinct microenvironments, which likely define their functional properties, such as immunomodulation. Here, we show in a lymphangiogenic murine melanoma model that LECs upregulate the enzyme Ch25h, which catalyzes the formation of 25-hydroxycholesterol (25-HC) from cholesterol and plays important roles in regulating lipid metabolism, gene expression, and immune activation. LECs represent the main source of extracellular 25-HC in tumors, leading to the inhibition of PPAR-g in intra-tumoral macrophages and monocytes. This prevents their immunosuppressive phenotype and instead promotes their conversion into proinflammatory myeloid cells that support effector T cell functions. We identify here in mechanistic detail a novel LEC function that supports anti-tumor immunity, which can be therapeutically exploited in combination with immunotherapy.
Biography
S. Hugues obtained her PhD in immunology in 2002. After a post-doc at the Curie Institute (Paris) in the laboratory of Sebastian Amigorena, she obtained a CR1 INSERM position in 2006. She joined the laboratory of Prof. Walter Reith at the Department of Pathology and Immunology, Faculty of Medicine, Geneva in 2008 as Maître-Assistant. She was awarded SNF Assistant Professor in 2010, obtained an ERC starting grant in 2012, and is Associate Professor since 2016. She received the Leenaards prize in 2011 and 2017.
Her work studies how the inflammatory environment impacts stromal cell plasticity and T cell responses in mouse models of tumors and autoimmune diseases.
17 Aug 2023