Kurzfassung

Recent insights into the mechanisms of immune suppression highlighted the immunological parallels between cancer and chronic infections, which can be used to better understand the underlying pathologies, but also to define novel therapeutic avenues.

Regulatory T cells (Tregs) belong to the suppressive branch of the immune system controlling immune homeostasis under steady-state conditions. However, their ability to suppress other immune cells and to establish peripheral immune tolerance can...Recent insights into the mechanisms of immune suppression highlighted the immunological parallels between cancer and chronic infections, which can be used to better understand the underlying pathologies, but also to define novel therapeutic avenues.

Regulatory T cells (Tregs) belong to the suppressive branch of the immune system controlling immune homeostasis under steady-state conditions. However, their ability to suppress other immune cells and to establish peripheral immune tolerance can be detrimental to the immune response against cancerous or infected cells. In cancer, Tregs are associated with increased tumor progression and reduced therapy response rates in mice and humans. Therefore, overcoming the Treg-mediated suppressive barrier in the tumor to enhance anti-tumor immune responses is of central interest to further improve cancer immunotherapy. In this study, we introduce a bacteria-derived metabolite as a molecule to modulate the differentiation and function of Tregs and bolster anti-tumor immunity. We show that this specific metabolite interferes with iTreg differentiation and rewires their metabolic state in vitro by interfering with the expression of the transcription factor FoxM1. Using the mouse model of B16 melanoma, we demonstrate that this metabolite reduces the frequency of FoxP3+ cells within the tumor microenvironment. Strikingly, tumor-infiltrating Tregs in metabolite-treated mice display a pro-inflammatory profile, expressing more TNF-α and IFN-γ than those in control mice. Therefore, we propose that this metabolite has the potential to boost anti-tumor immunity by directly modulating the host anti-tumor immune response and should be further investigated not only in tumor models but also in chronic infections.» weiterlesen» einklappen