Advances in three-dimensional hydrogel networks for cancer immunotherapy

Cancer immunotherapies, including chimeric antigen receptor (CAR) T-cell and immune checkpoint blockade (ICB) therapy, have revolutionized oncological treatment. However, suboptimal patient response rates and immune-related adverse events continue to pose significant clinical challenges. The immunosuppressive tumor microenvironment (TME) is a critical factor influencing immunotherapy efficacy and it can impede immune cell infiltration and functionality. Three-dimensional (3D) hydrogel networks offer a promising approach to modulating the immunosuppressive characteristics of the TME by targeting and responding to its distinct physicochemical properties, such as aberrant acidity, hypoxia, elevated reactive oxygen species (ROS) levels, irregular vasculature, and a dense extracellular matrix (ECM). This review summarizes recent advances in hydrogel-based cancer immunotherapy, providing insights into refining targeted immunotherapeutic strategies to enhance anti-tumor immune responses. It explores hydrogel-based immunotherapy strategies designed to modulate these characteristics within tumors, aiming to improve the efficacy of diverse immunotherapeutic approaches. It begins by outlining the opportunities associated with hydrogel-facilitated immunotherapy. Subsequent sections describe the advantageous properties of hydrogels for cancer immunotherapy, including immune cell-based therapy, combinatorial approaches, targeted therapy, and vaccines using hydrogel matrices. We discuss how hydrogel platforms unlock previously unattainable avenues for immunotherapy. Finally, we discuss future outlooks and research directions in this rapidly evolving field.