Polymeric Materials in Cancer Immunotherapy: Advances, Challenges, and Future Directions

Despite revolutionary advances in tumor immunotherapy, its efficacy is often limited by antigen heterogeneity, immune exhaustion, and impaired immune cell infiltration caused by the immunosuppressive tumor microenvironment (TME). Polymer nanocarriers, leveraging their tunable physicochemical properties, modular architecture, and high design flexibility, offer an ideal platform to overcome these bottlenecks. They can not only protect immunotherapeutic agents (e.g., antigens, adjuvants, checkpoint inhibitors) and enable their targeted and controlled release but also enhance antigen presentation, reinvigorate effector immune cell functions, and reprogram the immunosuppressive network through spatiotemporally precise immune regulation. Furthermore, the versatility of polymer platforms empowers various cutting-edge therapeutic modalities, including cancer vaccines, adoptive cell therapies, and oncolytic viruses, demonstrating broad application potential. This review systematically explores the design principles and targeting strategies of polymer materials for tumor immunotherapy, their key roles in modulating anti-tumor immunity, and the core challenges in their clinical translation. Finally, this review envisions a new intelligent research paradigm driven by artificial intelligence (AI)-aided design and validated by clinically relevant systems such as humanized animal models to accelerate the development of next-generation polymer-based immunotherapies.