In situ antigen-capture strategies for enhancing dendritic cell-mediated anti-tumor immunity

Abstract

Dendritic cell (DC)-mediated tumor immunotherapy has demonstrated considerable potential, effectively bridging tumor antigens with specific anti-tumor immune responses. However, the heterogeneous and immunosuppressive tumor microenvironment (TME) frequently impairs DC function by inhibiting antigen uptake, restricting differentiation into mature DCs (mDCs), and limiting migration to tumor-draining lymph nodes (TDLNs), ultimately resulting in immune tolerance that diminishes specific anti-tumor immune responses. To overcome these limitations and effectively restore the DC-mediated link between tumor-derived antigens and robust anti-tumor immunity, nanovaccines utilizing in situ antigen-capture strategies have been developed. These strategies uniquely offer personalized and targeted activation of anti-tumor immune responses. In this review, we first address the influence of the TME on DC functionality, highlighting the numerous immunosuppressive factors that restrict efficient antigen uptake by DCs. Subsequently, we detail the core mechanisms underlying in situ antigen-capturing nanovaccines (AC-NVs), including covalent, noncovalent, and combined antigen capture methods. Furthermore, recent advances in AC-NVs constructed from various biomaterials are reviewed, emphasizing their intrinsic material properties and antigen-capturing capabilities for functionalizing DCs and enhancing specific anti-tumor immunity. Finally, we discuss current challenges and future perspectives for AC-NVs, emphasizing their potential role in developing personalized cancer vaccines, optimizing immune responses, and facilitating clinical translation.