Etude du rôle du récepteur de l’IL-22 et de sa partie C-terminale dans le développement tumoral du cancer du pancréas
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- Pancreatic cancer is characterised by its aggressiveness and increasing incidence, partly linked to lifestyle factors. With an estimated 5-year survival rate of less than 10%, it is predicted to become the second leading cause of cancer-related death by 2030. Its development often occurs asymptomatically, resulting in late diagnosis and limited therapeutic approaches. One of the key factors involved in tumour development is inflammation, which creates a microenvironment conducive to tumour initiation and progression. Cytokines are key mediators of inflammation and are potential therapeutic targets. In this thesis, we focus on one specific cytokine called interleukin-22 (IL-22). Unlike other cytokines, IL-22 acts on epithelial cells. It plays a crucial role in epithelial repair and protection against pathogens. Il-22 is also studied in tumour development due to its role in cell survival and proliferation. To exert its function, IL-22 acts on its receptor IL-22R composed of the IL-22Rα and IL-10Rβ chains. Binding of IL-22 to its receptor triggers two distinct pathways: the classical tyrosine-dependent pathway and the alternative tyrosine-independent pathway which requires the C-terminal part of the receptor. While the pancreas exhibits the highest levels of IL-22R expression among organs, few studies have focused on its role in pancreatic cancer. Therefore, our aim was to investigate the role of IL-22R and its C-terminal part in pancreatic cancer tumorigenesis. To do this, we used a murine model involving orthotopic injection of KPC792 cancer cells. We found that the absence of IL-22R in Il22ra1-/- mice or its inhibition via injection of blocking anti-IL-22Rα antibodies did not influence tumour growth in our model. We also examined the effect of injecting KPC792 in which the whole receptor or its C-terminal part is deleted, generated by CRISPR-Cas9, in tumorigenesis. However, our findings revealed substantial variability among the different clones. Finally, injection of IL-22 did not induce a difference in the size of tumours developed by the mice. Taken together, these results suggest that the IL-22/IL-22R axis does not impact tumour development in our model. However, this model specifically addresses the role of IL-22 and its receptor on tumour growth. Further investigation of their involvement in early and late stages of pancreatic cancer development is thus needed.
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Dhulst, L. (2024). Etude du rôle du récepteur de l’IL-22 et de sa partie C-terminale dans le développement tumoral du cancer du pancréas. https://dial-mem.test.bib.ucl.ac.be/handle/2078.2/37273