Dissertation defence (Medical Microbiology and Immunology): MSc Karolina Losenkova Mingeaud

MSc Karolina Losenkova Mingeaud defends the dissertation in Medical Microbiology and Immunology titled “Adenosine metabolism in cancer: unveiling new therapeutic opportunities” at the University of Turku on 7 March 2025 at 12.00 (University of Turku, Biocity, Ministeri Auditorium, Tykistökatu 6 A, Turku).

Opponent: Professor Simon Robson (Harvard University, USA)
Custos: Professor Sirpa Jalkanen (University of Turku)

Doctoral Dissertation at UTUPub: https://urn.fi/URN:ISBN:978-952-02-0049-7

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Summary of the Doctoral Dissertation:

Adenosine triphosphate (ATP) and its derivative, adenosine, are fundamental to cellular function. ATP serves as the primary cellular energy source, while adenosine is a building block for DNA and RNA synthesis. Beyond their intracellular roles, both molecules act as extracellular signaling molecules that regulate various physiological processes, including immune responses. When ATP is released into the extracellular space, enzymes CD39 and CD73 degrade it into adenosine. This adenosine then binds to specific receptors on immune cells, suppressing their activity. Cancer cells exploit this pathway to evade immune detection. As a result, therapies targeting CD39, CD73, or adenosine receptors have been developed to counteract tumor-induced immunosuppression, though their limited clinical success underscores the need for a deeper understanding of adenosine metabolism in the tumor microenvironment.

While CD39 and CD73 are well-known players in ATP and adenosine metabolism, they are not the only ones. Other metabolic pathways also regulate ATP and adenosine levels outside cells but are often overlooked. This dissertation examines the broader network of enzymes involved in ATP and adenosine metabolism across different human cell types. Vascular endothelial cells, cancer cells, and T cells studied in this work each exhibit a unique set of these enzymes and adapt their activity differently in response to hypoxia and other environmental challenges.

Another key aspect of this research is intracellular adenosine metabolism. Cells can take up extracellular adenosine and metabolize it internally. While much attention has been given to adenosine’s signaling function outside cells, the significance of its intracellular metabolism remains largely unexplored. This work reveals that, upon uptake, adenosine can strongly suppress T-cell growth and function, providing new insights into the immunosuppressive role of adenosine independent of its receptors.

Taken together, this dissertation enhances the understanding of the heterogeneous nature of adenosine metabolism within the tumor microenvironment, while also highlighting the importance of intracellular adenosine metabolism. These findings could help guide the development of more effective cancer therapies, ultimately benefiting cancer patients.
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