Getuigenis: Veronica De Simone PhD - Fundamental Mandates, laureaten 2019

My name is Veronica De Simone and I work as postdoctoral researcher at KU Leuven.

Thanks to the generosity of many donors, Stichting tegen Kanker provided me a financial support to devote my studies to the fight against cancer.

This fellowship will provide me with a unique opportunity to further develop my long-standing interest in oncoimmunology and to apply my knowledge to detect the molecular mechanisms involved in in colon cancer pathogenesis and progression.

Colorectal cancer (CRC) is one of the most common malignancies, ranking third in the world with respect to number of patients affected in their lifetime. A recent prediction estimated that by 2030 we will have more than 2.2 million new cases of CRC with 1.1 million deaths worldwide. In Belgium 10.000 new invasive CRC cases have been diagnosed in 2018.

Although  innovative technologies have had a significant impact on the diagnosis, surgery and therapy of CRC, patients with advanced disease still have a very poor prognosis due to the inefficacy of common anti-cancer therapies. This is in part due to the fact that colorectal cancer is a rapidly evolving neoplasm acquiring several mutations and increasing complexity of the tumor microenvironment leading to resistance to both standard and targeted therapeutics.

Nowadays, it is clear that apart from epithelial malignant cells, the colonic tumor microenvironment is populated by resident cells such as stromal and endothelial cells and recruited immune cells supporting tumor growth and invasiveness.

While the interaction between cancer cells and immune cells, including TAMs, has well been established, the presence and role of innervation in the colonic tumor microenvironment represent and unexplored field. I have obtained preliminary data suggesting  a striking up-regulation of enteric glial, the largest component of the enteric nervous system (ENS) and macrophage markers in patients with advanced disease. In addition, I have observed an intense crosstalk between enteric glia and TAMs in colonic tumors. Nerve infiltration in tumors is determined by the release of neurotropic growth factors by both cancer cells and immune cells, including macrophages. This evidence suggests that neuro-immune interaction in the tumor microenvironment may be an overlooked process involved in cancer progression.

Thus, I hypothesize that, in CRC, the enteric nervous system may be responsible for the accumulation and differentiation of TAMs, resulting into tumor progression.

The main objective of my project is to elucidate and interfere with molecular pathways governing the crosstalk between enteric glial cells and TAMs to prevent tumor growth and progression.

Finally, I aim to identify novel targets for potential therapeutic intervention and will develop innovative proof-of-concept tools to improve CRC prognosis and treatment.

I strongly believe that the success of my project will provide a first step towards the development of novel therapeutics useful for a large panel of tumors and not only for colorectal cancer.