Dendritic cells (DCs) are equipped for sensing danger signals and capturing, processing, and presenting antigens to naive or effector cells and are critical in inducing humoral and adaptive immunity. Successful vaccinations are those that activate DCs to elicit both cellular and humoral responses, as well as long-lasting memory response against the target of interest. Recently, it has become apparent that tumor cells can provide new sources of antigens through nonsynonymous mutations or frame-shift mutations, leading to potentially hundreds of mutation-derived tumor antigens (MTAs) or neoantigens. T cells recognizing MTA have been detected in cancer patients and can even lead to tumor regression. Designing MTA-specific vaccination strategies will have to take into account the adjuvant activity of DC subsets and the best formulation to elicit an effective immune response. We discuss the potential of human DCs to prime MTA-specific responses.