Development of an in vitro 3D model system for testing PD-1/PDL-1 immune checkpoint inhibitors

Background: Immune checkpoint inhibitors provide a new hope for cancer patients not responding to chemotherapy by removing the tumor protection against immune cell attacks. Nevertheless, only a subset of patients responds well to these therapies, and recent studies demonstrated that the mechanisms of action are more complex than expected, often involving multiple cell types of the immune system. Importantly, for a better understanding and assessment of immune cell eliciting cell tumor death, there is a need to have fully human, complex 3D in vitro models. We developed a 3D tumor-immune cell coculture model and show here acquired insights on the modulatory capacity of immune checkpoint inhibitors. In the present study we have developed a 3D tumor - immune cell coculture model and evaluated its application to study the effect of immune checkpoint inhibitors on tumor viability, cytokine secretion, and immune cell infiltration.