The Use of Human Dendritic Cell Subsets in Cancer Vaccines
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Dendritic cells (DC) have been used as therapeutic tools in cancer vaccines for more than a decade. The majority of clinical trials conducted in this field of immunotherapy have employed DC generated ex vivo from monocytes (moDC), as these DC can be easily propagated into large numbers. However, the clinical efficacy of moDC-based vaccines has remained unsatisfactory, as the laborious culturing protocols lead to exhaustion of their immunostimulatory capacity. Novel therapeutic strategies seek to capitalize on the distinct biological functions of naturally occurring DC subsets, i.e. myeloid DC (mDC) and plasmacytoid DC (pDC). Present in the skin, blood and secondary lymphoid organs, these subsets are capable of eliciting potent anti-tumour responses. Each subset has a specified effect on the immune system, and especially skin mDC and pDC are of interest for their capacity to induce tumour regression. Although natural DC subsets do not require extensive culturing periods, they are low in frequency and complicated isolation techniques are required to obtain them in sufficient number and purity. However, in vivo targeting techniques and identification of vaccine adjuvants that provide potent activation stimuli are promising developments. Combination therapies with conventional anti-cancer drugs can be considered to overcome the tolerogenic immune environment and stimulate efficient anti-tumour immunity.