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Tumor Models Developed To Test Different Treatments

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Each tumor is different, each patient is different. So how do you know which treatment will be best for the sick person and will be successful in eradicating their cancer? In order to offer a personalized treatment that best matches the case being treated, a team of scientists led by the University of Geneva (UNIGE) had already developed a spheroidal reproduction of tumors that integrates tumor cells, but also their microenvironment. However, the immune system was not yet taken into consideration, although it can either be strengthened or destroyed by the treatment offered to patients. Today, the Geneva team has succeeded in integrating into the spheroidal structure two types of immune cells that come directly from the sick person, allowing to test the various possible treatments and to select the most effective. Results to read in the journal Cancers .

In order to test cancer treatments, scientists use 2D cultures of cancer cells. 
However, these are only an artificial system, as they do not represent the tumor in 3D in all its complexity. This is why the team of Patrycja Nowak-Sliwinska, professor in the Pharmaceutical Sciences Section of the Faculty of Sciences at UNIGE, has developed a spheroidal structure that mimics the microenvironment of the tumor. "It's about creating a 3D structure from the tumor cells, also integrating fibroblasts - cells that make up the mass of the tumor - and endothelial cells, which allow the tumor to feed. and to be vascularized. »This method, since used by the University Hospitals of Geneva (HUG), allows you to get closer to the tumor present in the patient's body. "However, an important factor was still missing: the cells of the immune system", specifies the Geneva researcher.

The determining role of the immune system in the fight against cancer


Indeed, the immune system is the first fighter against tumors. And it reacts differently depending on the treatment prescribed to the sick person: it can either see its effectiveness increased tenfold, or reduced. Today, the Geneva team, in collaboration with the universities of Lausanne and Amsterdam, has succeeded in integrating two types of immune cells into its spheroidal structure: macrophages and T lymphocytes. test the effects of a treatment on the tumor, but also on the immune system! ”enthuses Magdalena Rausch, researcher at the Pharmaceutical Sciences Section of UNIGE and first author of the study. To do this, the scientists first take the tumor cells from the patient to recreate it in vitro in the form of a spheroidal structure, then they isolate the immune cells to inject them into the 3D structure. “Once this step has been carried out, which takes 24 hours, we can test the different possible treatments for this cancer on our tumor reproduction and study which one will best suit the sick person, taking into account its effects on the tumor cells, but also on the immune system, ”says Patrycja Nowak-Sliwinska.

This relatively inexpensive and rapid technique would make it possible to offer personalized treatment for each sick person, while offering an effective alternative to certain animal model experiments. "This platform opens up many possibilities for us to test drug combinations taking into account the different types of cancer, their mutations and the immune reactions specific to each person treated", concludes Patrycja Nowak-Sliwinska.

Reference: Rausch M, Blanc L, De Souza Silva O, Dormond O, Griffioen AW, Nowak-Sliwinska P. Characterization of renal cell carcinoma heterotypic 3D co-cultures with immune cell subsets. Cancers. 2021;13(11):2551. doi: 10.3390/cancers13112551

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