The role of the tumor microenvironment in tumors of the upper gastrointestinal tract

In recent years it has become evident that the tumor microenvironment is a key player in the development, resistance and progression of solid tumors. Esophageal adenocarcinoma and pancreatic ductal adenocarcinoma are both tumors of the upper gastrointestinal tract with a very high mortality. Moreover, they are characterized by an abundance in cells and proteins surrounding the tumor cells, the so-called tumor microenvironment. In this thesis, we have aimed to unravel the role of the tumor microenvironment in tumors of the upper gastrointestinal tract. We revealed that it can serve as a biomarker for prognosis as well as a target for tailored treatment, and identified ways to improve multimodality treatment directed against both tumor cells and the tumor microenvironment. Importantly, we obtained new insights into the extensive cross-talk between the intratumoral compartments (i.e. tumor cells, extracellular matrix, (myo)fibroblasts and blood vessels). It shows that when changes are made to one compartment of the tumor, this effect can be impaired or fortified by other compartments depending on patient-specific characteristics. This complex interaction is decisive for tumor development and therapy response. The results presented in this thesis provide a deeper understanding of the role of the tumor microenvironment in tumors of the upper gastrointestinal tract. For future purposes, a balance should be sought for the targeting of each compartment in these tumor types where maximum therapy efficacy is achieved.