Cancer remains one of the world's major health problems. In Europe, approximately 3.5 million new cases are diagnosed each year and nearly 2 million people die from cancer. It is estimated that the number of cases diagnosed annually will increase to more than 4 million in the next 10 years. More than 95% of cancers are solid tumours. Despite small advances in cancer treatment, the survival rate for solid tumours has not changed significantly in recent decades. In a new scenario where personalised medicine represents new strategies, immunotherapy has emerged as a promising field.
The immune system consists of a collection of cells with a high ability to migrate that work together to remove harmful foreign material from the body. Each immune cell can migrate between tissues, fulfilling specific functions in different microenvironments. However, this immune-surveillance response is not very effective in solid tumours, which are tissues with a high non-physiological stiffness and a significant level of residual stresses. Understanding the mechanisms that govern the cellular immune response to solid tumours is crucial to strengthen the development of novel immunotherapies.
ICoMICS aims to develop a novel predictive modelling platform to investigate how therapeutic immune cells (TICs) sense, migrate and interact with cancerous cells and with the tumor microenvironment (TME). This platform will be built on two key pillars: in-vitro 3D tumor organoids and multicellular simulations, which will be combined and integrated by means of machine learning algorithms. On the one hand, cell culture microfluidic chips will be microfabricated, allowing continuous perfusion of chemical modulators through hydrogels (including decellularized matrices) inhabited by human tumour cells arranged to recreate 3D solid tumor organoids (Objective 1). On the other hand, an agent-based model will be developed to simulate cells, including cell-cell and cell-matrix interactions, combined with a continuum approach to model matrix mechanics and chemical reactions of cells, such as reactive oxygen species (ROS) and nutrients diffusion (Objective 2). The ICoMICS platform will, therefore, provide a modelling approach capable of predicting how therapeutic immune cells will migrate and interact with the tumour microenvironment, helping to develop novel immunotherapy-based treatments (Objective 3).
All this research will be applied to three main solid tumours: lung, liver and pancreas.
