In recent years, the tumor microenvironment (TMM) has been identified as an important factor in tumor initiation, progression, metastasis, and the development of (chemo)therapy resistance.
The modification of tumor properties is achieved through multidirectional exchange between the tumor cell network and the cells of the surrounding tissue. Whether certain TMM components have tumor-promoting or tumor-inhibiting properties depends on the cell type of the TMM, the tumor entity, and the tumor stage.
The components of the TMM include mesenchymal stromal cells (MSCs), fibroblasts, and immune cells. A deeper understanding of the interaction mechanisms between the cells of the TMM and the tumor is necessary in order to develop innovative approaches for tumor treatment and to overcome resistance to therapy.
This is also where modern immunotherapies, known as immune checkpoint inhibitors, come into play. Unlike systemic chemotherapy, these immunotherapies have the great advantage of targeting tumors more precisely and causing fewer side effects. However, there are currently only a few types of cancer for which these new treatment options can be used.
Another challenge is that only about 25% of patients benefit from immune checkpoint inhibitors. The reasons for this have hardly been researched to date. In order to develop future and improved treatment options, it is essential to cultivate tumor cells and TMM cells together so that they can interact directly. Afterwards, tumor cells and cells of the tumor microenvironment must be separated from each other precisely and gently in order to examine them separately. High-throughput analyses are indispensable for this purpose. We have already established and analyzed the spheroid cultures required for this. To do this, we cultivated and analyzed tumor cells from urothelial carcinoma and MSCs together. This approach has already yielded promising results.
In order to validate these results and to test whether they are suitable for possible future therapy, we need to carry out further extensive analyses. In addition, further experiments with spheroids from tumor cells, fibroblasts, and immune cells are planned.