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Inhibition of tumor-associated regulatory T cells by microbial metabolites

Laufzeit: 01.01.2020 - 31.12.2021

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Kurzfassung


Cancer is a leading cause of death in the western European hemisphere and will most likely increase in the next years due to an aging society. Despite recent advances in cancer treatment options, new alternative strategies are still urgently needed. Cancer can manipulate its microenvironment to favor immune cells that support its own growth and inhibit anti-tumor immune responses. One of the immune cell types predominantly observed in cancer tissues are regulatory T cells (Tregs). Tregs...Cancer is a leading cause of death in the western European hemisphere and will most likely increase in the next years due to an aging society. Despite recent advances in cancer treatment options, new alternative strategies are still urgently needed. Cancer can manipulate its microenvironment to favor immune cells that support its own growth and inhibit anti-tumor immune responses. One of the immune cell types predominantly observed in cancer tissues are regulatory T cells (Tregs). Tregs harbor multiple mechanisms that inhibit immune responses in the body and are needed to establish peripheral tolerance. Still, during tumor progression their ability to suppress cytotoxic T Lymphocytes (CTLs) and T helper cell (Th) responses hinders the eradication of cancer cells. There is an unmet medical need to specifically inhibit Tregs in cancer. Recently, we have discovered that pro-inflammatory Th cells and anti-inflammatory Tregs differ in their metabolic requirements related to fatty acid metabolism and can be therapeutically modulated with small natural compounds derived from bacteria. We now identified a new bacteria-derived compound, as an inhibitor of murine Treg differentiation in vitro and preliminary data demonstrate that treatment with this metabolite decreased tumor burden and improved overall survival in a mouse model of melanoma. We plan to study the potential of this microbial substance as an immunomodulatory drug targeting Tregs in vivo using different murine cancer models and to dissect the molecular mechanism of action. This approach may pave the way for new immunomodulatory drugs for cancer therapy targeted directly towards Tregs and will help us to better understand the molecular mechanisms controlling Treg development and function.» weiterlesen» einklappen

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