The scheme of DC-based cancer immunotherapies. (A) Direct activation of DCs by the administration of several molecules, such as FLT3-LG, GM-CSF, and poly I:C variants, is one strategy of DC-based immunotherapies. In addition, it is the other strategy to genetically engineer tumor cells to produce GM-CSF. (B) Together with DC activation, the administration of tumor-derived antigens induces DCs to promote tumor-specific immune responses. Tumor-derived antigens can be delivered as whole-tumor lysates or specific antigens including neoantigens, which are predicted by next generation sequencing and bioinformatic tools. (C) For DC vaccine, immature DCs, which are conventional DCs or moDCs, are isolated from the peripheral blood of cancer patients, and these cells are maturated and activated with tumor antigens as tumor lysates or specific antigens. In order to improve the functionality, DCs are engineered by using genetical tools, such as the CRISPR-Cas9 system and viral vectors. Then, activated DCs loaded with tumor antigens are reinfused into patients, leading to the induction of an antigen-specific immune response. Since immunosuppressive TME might deteriorate the efficacy of a DC vaccine, ICB therapies are combined with DC vaccine in order to reverse TME.
