Although cancer vaccines have yielded promising results both in vitro and in animal models, their translation into clinical application has not been very successful so far. Through the success of immune checkpoint inhibitors, the tumor immunotherapy field revived and led to important new insights. A better understanding of the functional capacity of different dendritic cell (DC) subsets and the immunogenicity of tumor antigens, more particularly of neoantigens, have important implications for the improvement of cancer vaccines. These insights can guide the development of novel strategies, to enhance the clinical utility of cancer vaccines. The aim of this Research Topic was therefore to provide a comprehensive overview of current issues regarding cancer vaccine development with an emphasis on novel approaches toward enhancing their efficacy.