For several years, cancer cells from individual patients have been cultivated as so called "organoids". This form of cell culture, where the cancer cells grow in three-dimensional structures similar to those found in the body, preserves many of the cancer cell's original properties and allows doctors and researchers to assess the effectiveness of therapies for individual patients. Organoids are therefore a valuable alternative to traditional cell cultures. However, these cultures alone were not able to reliably predict the response to commonly used colorectal cancer therapies.
The MedUni Vienna-based research team has made a breakthrough by adding fibroblasts and monocytes to the organoid culture. Fibroblasts provide structure to both healthy and cancerous tissues, and monocytes are immune cells that differentiate into macrophages in the tissue and tumor, where they should contribute to initiating anti-tumoral immune responses. The team has demonstrated that these three cell types communicate with each other in the petri dish in a manner similar to what is observed in the body. "This new model system now allows researchers to study the therapeutic effects on the immune system in the context of personalized medicine," reports Michael Bergmann (Department of General Surgery, MedUni Vienna/AKH Wien).
More precise statements about individual cancer tissue
The team was also able to demonstrate, for the first time, that certain chemotherapies that have negative long-term effects on the immune system can actually lead to activation of the macrophages in the short term. "This new system allows for much more accurate assessments of the properties of individual, patient-specific tumor tissue," adds Matthias Farlik (Department of Dermatology, MedUni Vienna/AKH Wien). In the future, so the researcher, these advancements could lead to the development of personalized therapies for colorectal cancer patients. Moreover, the team is now able to test novel immunotherapies designed to support the immune system in fighting cancer, and they are optimistic that these advances will lead to improved treatment outcomes in the field of personalized medicine.
Publication: Journal for ImmunoTherapy of Cancer
Cancer-associated fibroblasts shape early myeloid cell response to chemotherapy-induced immunogenic signals in next generation tumor organoid cultures.
Julijan Kabiljo, Anna Theophil, Jakob Homola, Annalena F Renner, Nathalie Stürzenbecher, Daphni Ammon, Rebecca Zirnbauer, Simone Stang, Loan Tran, Johannes Laengle, Askin Kulu, Anna Chen, Markus Fabits, Velina S Atanasova, Oliver Pusch, Wolfgang Weninger, Henning Walczak, Dietmar Herndler Brandstetter, Gerda Egger, Helmut Dolznig, Anna Kusienicka, Matthias Farlik, Michael Bergmann.
doi: 10.1136/jitc-2024-009494
https://jitc.bmj.com/content/12/11/e009494