Advanced Microfluidic Models of Cancer and Immune Cell Extravasation: A Systematic Review of the Literature

Extravasation is a multi-step process implicated in many physiological and pathological events. This process is essential to get leukocytes to the site of injury or infection but is also one of the main steps in the metastatic cascade in which cancer cells leave the primary tumor and migrate to target sites through the vascular route. In this perspective, extravasation is a double-edged sword. This systematic review analyzes microfluidic 3D models that have been designed to investigate the extravasation of cancer and immune cells. The purpose of this systematic review is to provide an exhaustive summary of the advanced microfluidic 3D models that have been designed to study the extravasation of cancer and immune cells, offering a perspective on the current state-of-the-art. To this end, we set the literature search cross-examining PUBMED and EMBASE databases up to January 2020 and further included non-indexed references reported in relevant reviews. The inclusion criteria were defined in agreement between all the investigators, aimed at identifying studies which investigate the extravasation process of cancer cells and/or leukocytes in microfluidic platforms. Twenty seven studies among 174 examined each step of the extravasation process exploiting 3D microfluidic devices and hence were included in our review. The analysis of the results obtained with the use of microfluidic models allowed highlighting shared features and differences in the extravasation of immune and cancer cells, in view of the setup of a common framework, that could be beneficial for the development of therapeutic approaches fostering or hindering the extravasation process.