Jingwen Wang, Xibiao Jia, Yaxin Zhang, Xiaoyu Wang, Yunhai Fu, Zhiyao He
Dendritic cells (DCs), as the most protent professional antigen-presenting cells (APCs), possess an exceptional capacity to initiate and modulate adaptive immune responses, rendering DC-based vaccines a highly promising approach in tumor immunotherapy. This review explores the biological properties of DCs, establishing a foundation for the rational development of DC vaccine. We further provide a comprehensive overview of current mainstream DC vaccine platforms, with analysis of three representative strategies: (i) DC vaccines loaded with tumor lysates; (ii) personalized neoantigen-pulsed DC vaccines; and (iii) DC-derived exosome vaccines, a rapidly emerging cell-free therapeutic modality. With respect to clinical translation, we summarize the outcomes of clinical trials conducted over the past five years, particularly targeting high-mortality malignancies. While the results are encouraging, the broad clinical application remains limited, posing several challenges, including functional heterogeneity of DCs and immunosuppressive tumor microenvironment, which need to be overcome. Combination strategies, such as DC vaccination paired with chemotherapy, radiotherapy or immune checkpoint blockade, are increasingly recognized as essential for enhancing therapeutic efficacy. With the sustainable progress in tumor immunobiology and advanced bioengineering in the future, the development of DC vaccines will be accelerated, offering novel therapeutic prospects for patients with refractory cancers.