Engineering the fate and function of human T-Cells via 3D bioprinting

T-cell immunotherapy holds promise for the treatment of cancer, infection, and autoimmune diseases. Nevertheless, T-cell therapy is limited by low cell expansion efficiencyex vivoand functional deficits. Here we describe two 3D bioprinting systems made by different biomaterials that mimic thein vivoformation of natural lymph vessels and lymph nodes which modulate T-cell with distinct fates and functions. We observe that coaxial alginate fibers promote T-cell expansion, less exhausted and enable CD4⁺T-cell differentiation into central memory-like phenotype (Tcm), CD8⁺T-cells differentiation into effector memory subsets (Tem), while alginate-gelatin scaffolds bring T-cells into a relatively resting state. Both of the two bioprinting methods are strikingly different from a standard suspension system. The former bioprinting method yields a new system for T-cell therapy and the latter method can be useful for making an immune-chip to elucidate links between immune response and disease.