PM.20.055 – iChip: next generation models for cancer immunotherapy

Immunotherapy is gaining ground in clinical oncology, and it is increasingly recognized that the surroundings of the tumor, i.e. the tumor micro-environment (TME), play a crucial role in determining the success rate of this treatment. The interaction between tumor cells and the TME is affected by its cellular components, metabolism, blood supply and physical barriers and cannot be investigated to its full extent in current in vitro or mouse models. Our aim is therefore to develop highly physiological, TME-reconstituted, 3D organotypic human melanoma- and breast cancer-on-a-chip (CoC) models. Melanoma is highly responsive to immunotherapy, while breast cancer represents a heterogeneous tumor type which responds much less favorably to current immune therapies. These two models allow us to investigate how key components of the TME affect these different therapeutic responses. We have built a consortium covering experts in the field of cancer biology, onco-immunology, metabolism, physical propertiestissue mechanics, matrix remodeling and imaging, microfluidics and fabrication. We expect that the highly representative human CoC models developed here will provide innovative predictive methods which greatly facilitate the delineation of molecular and cellular processes underlying failure of immunotherapy, and consequently enable the study into drugs blocking the diverse modes of immune suppression.

Keywords

Breast cancer, extracellular matrix, immune micro-environment, melanoma, microfluidics