Dear Colleagues,

As the sentinels of the immune system, dendritic cells (DCs) play a critical role in initiating and regulating antigen-specific immune responses. Cross-priming, a process in which DCs activate CD8 T cells by cross-presenting exogenous antigens onto their MHC class I (MHCI), plays a major role in mediating CD8 T cell immunity and tolerance. Exploiting their ability to potentiate host effector and memory CD8 T cell responses critical for anti-tumor immunity, DC vaccines have emerged as one of the leading strategies for cancer immunotherapy. DCs include heterogeneous populations such as conventional DCs (cDCs), plasmacytoid DCs (pDCs), and monocyte-derived DCs (MoDCs). DC vaccines, of which the majority employ MoDCs generated in vitro, are largely unsuccessful, only achieving objective immune responses in 5-15% of patients. Despite largely disappointing clinical trials, the promising results from DC vaccine clinical trials using neoantigens offer an exciting new development on DC cancer vaccines. The recent discovery onfthe critical role of cDC1s (type 1 conventional DCs) in cross-priming tumor antigen-specific CD8 T cells and in determining the efficacy of cancer immunotherapies further highlighted the importance of the development and refinement of DC-based vaccines either as monotherapy or combinational immunotherapies.

There are two major hurdles to the success of DC-based vaccines: tumor-mediated immunosuppression and the functional limitations of the commonly used in vitro differentiated DCs. Vaccines with DC-derived exosomes (DCexos), which are nano-sized inert vesicles resistant to regulation by tumor-related factors compared to DCs, have been heralded as the superior alternative cell-free therapeutic vaccines over DC vaccines. In vivo DC-targeted vaccines and the use of naturally circulating blood DCs also offer promising alternatives to in vitro cultured DCs. There are critical gaps in our understanding of even basic biology on these approaches, such as how DCexos and different subsets of DCs prime T cells, thus hindering their translation in clinical application. Similarly, there is a critical need for better understanding of how DCs interact with other DCs, B cells, and NK cells to fully unleash the potential of DC-based vaccines. Along the same line, more studies are required to best engineer/modify DCs/DCexos (e.g., miRNAs, mRNAs) to augment their function in anti-tumor immunity and improve anti-tumor efficacy.  

This Special Issue of Vaccines therefore welcomes new research articles and timely reviews on all aspects of dendritic cells and/or their role in cancer immunotherapy. 

Dr. Aimin Jiang
Dr. Li Zhou
Guest Editors

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• dendritic cells
• DC-based vaccines
• antigen presentation
• T cell responses