Specialiserade funktioner av lymfknutans kärl i reglering av immunsvar mot cancertumörer och spridning av cancer.

Tidsperiod: 2017-01-01 till 2020-12-31

Projektledare: Maria Helena Ulvmar

Finansiär: Vetenskapsrådet

Bidragstyp: Bidrag för anställning eller stipendier

Budget: 6 000 000 SEK

The lymph nodes provide a unique environment for immune activation and regulation, including antitumor responses. They arealso common sites for tumor metastasis. My own and others recent data has shownthat the blood and lymphatic vessels in the lymph nodes directly influence the immune response by expression of immunomodulatory genes in a remarkable site specific manner. This heterogeneity of the vessels and their role in immune regulation has earlier largely beenunknown. The overall aim of this project is therefore to uncover how specialized subsets of blood and lymphatic endotheliumin the lymph nodes are formed and how they function in regulation of the immune response in cancer. The experimental tools include advanced multicolor cell sortingto separatedifferenttypes of endothelial cells, in completely new ways, followed by RNAseq expression analysis. This will be combined with 3D imaging to spatially map vessels and their interaction with immune and cancer cells. The functional role of genes expressed by specific types of vesselswill be addressed using state-of-the-art genetic endothelial cell targeted mouse models in protocols of experimental cancer and immunotherapy. My long-term ambition is to identify new therapeutic strategies to promote effective anti-tumor immune responses but also find ways to interfere with metastatic disease. Beside cancer, our data will importantly also be of relevance for immune-mediated diseases such as allergy and autoimmune diseases.