Abstract
In response to growing clinical demands for more targeted and effective immunotherapies to treat cancer, biomaterial-based strategies have emerged as powerful tools for locally regulating immune responses. Among these, hydrogels, a class of biocompatible and tunable polymeric networks, are increasingly being leveraged for their high versatility and adaptability for creating tailored immune environments. By enabling controlled delivery of immune cues and direct cellular engineering, hydrogels utilized in vivo can precisely regulate both innate and adaptive immune responses while minimizing systemic toxicity. In this review, we outline essential hydrogel design features necessary for in vivo functionality including injectability, degradation kinetics, and immune-specific functionalization. Building on these principles, we explore how hydrogels have been employed to enhance T cell activation and dendritic cell maturation and guide macrophage reprogramming. Beyond cellular modulation, we further examine the use of hydrogels for cytokine and immunoregulatory agent delivery, tumor microenvironment remodeling, and the creation of tertiary-like lymphoid structures. Finally, we review recently completed and ongoing clinical trials of hydrogels in the cancer immunotherapy space. Together, these insights underscore the growing potential of in vivo hydrogel systems as immuno-interactive platforms capable of reshaping immune responses across diverse disease contexts.