Modeling the tumor immune microenvironment for drug discovery using 3D culture

A few decades ago, the notion that a patient's own immune system could recognize and eliminate tumor cells was highly controversial; now, it is the basis for a thriving new field of cancer research, cancer immunology. With these new immune-based cancer treatments come the need for new complex preclinical models to assess their efficacy. Traditional therapeutics have often targeted the intrinsic growth of cancer cells and could, thus, be modeled with 2D monoculture. However, the next generation of therapeutics necessitates significantly greater complexity to model the ability of immune cells to infiltrate, recognize, and eliminate tumor cells. Modeling the physical and chemical barriers to immune infiltration requires consideration of extracellular matrix composition, architecture, and mechanobiology in addition to interactions between multiple cell types. Here, we give an overview of the unique properties of the tumor immune microenvironment, the challenges of creating physiologically relevant 3D culture models for drug discovery, and a perspective on future opportunities to meet this significant challenge.