It is suggested that irreversible alterations occur in the cell of origin, which increase the cell’s’ tendency to cancer. The resultant variations could have adaptive advantages; nevertheless, as these changes accumulate over time, the risk of malignancy increases. At some point, the cellular proliferation rate increases, and the programmed cell death mechanism loses its accuracy and efficiency. The resulted cell mass affects the microenvironment (TME); hence, it could indirectly affect the physiology of the body. Alterations in the TME can inhibit or activate immune responses. The goal for cancer immunotherapy is to reactivate the disabled immune system to suppress tumor cells. One of the newly discovered cells of the immune system are dendritic cells (DCs), which have important roles in presenting antigens to lymphocytes, and are known as the major responsible cells in the activation of naïve T cells. As these cells are present in peripheral tissues, they appear to be one of the main targets of tumors’ direct or indirect effects. Therefore, one immunotherapy resolution is to reobtain mature DCs with the ability to present tumor antigens. In this chapter, to outline DCs’ therapeutic potentials and limits, mechanisms by which dendritic cells are affected by cancerous cells are explored. In addition, promises and challenges of the application of DCs in cancer immunotherapy are discussed.