Three-dimensional (3D) scaffolds as powerful weapons for tumor immunotherapy

Though increasing understanding and remarkable clinical successes have been made, enormous challenges remain to be solved in the field of cancer immunotherapy. In this context, biomaterial-based immunomodulatory strategies are being developed to boost antitumor immunity. For the local immunotherapy, macroscale biomaterial scaffolds with 3D network structures show great superiority in the following aspects: facilitating the encapsulation, localized delivery, and controlled release of immunotherapeutic agents and even immunocytes for more efficient immunomodulation. The concentrating immunomodulation in situ could minimize systemic toxicities, but still exert abscopal effects to harness the power of overall anticancer immune response for eradicating malignancy. To promote such promising immunotherapies, the design requirements of macroscale 3D scaffolds should comprehensively consider their physicochemical and biological properties, such as porosity, stiffness, surface modification, cargo release kinetics, biocompatibility, biodegradability, and delivery modes. To date, increasing studies have focused on the relationships between these parameters and the biosystems which will guide/assist the 3D biomaterial scaffolds to achieve the desired immunotherapeutic outcomes. In this review, by highlighting some recent achievements, we summarized the latest advances in the development of various 3D scaffolds as niches for cancer immunotherapy. We also discussed opportunities, challenges, current trends, and future perspectives in 3D macroscale biomaterial scaffold-assisted local treatment strategies. More importantly, this review put more efforts to illustrate how the 3D biomaterial systems affect to modulate antitumor immune activities, where we discussed how significant the roles and behaviours of 3D macroscale scaffolds towards in situ cancer immunotherapy in order to direct the design of 3D immunotherapeutic.