Fig. 5

Synthetic immune niches act locally to control the anti-cancer immune response. Current immunotherapeutic strategies are often delivered intravenously, resulting in systemic exposure to immunostimulatory agents and treatment-associated toxicity. These strategies include cellular immunotherapies that deliver either ex vivo–expanded immune cell (such as dendritic cells [DCs]) vaccination; adoptive T-cell therapy using tumor-infiltrating lymphocytes (TILs) or chimeric antigen receptor (CAR)-engineered T cells (upper left); or in vivo–acting nanovaccines, immune checkpoint inhibitors, and cytokines (lower left). By contrast, local administration of immunostimulatory agents may result in more effective treatment at lower doses while simultaneously preventing systemic toxicity. Applying synthetic immune niches for scaffold-based adoptive cell transfer (upper right) or scaffold-based cancer vaccination (lower right) not only enables local immunomodulation, but also may overcome other limitations of current immunotherapeutic interventions that are related to cell delivery and sustained availability of immunostimulatory agents (reprinted with permission from Ref [78]; © 2018 Nature Publishing Group)