The use of dendritic cells (DCs) to prime tumor-associated antigen-specific T cell responses provides a promising approach to cancer immunotherapy. Embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) can differentiate into functional DCs, thus providing an unlimited source of DCs. However, the previously established methods of generating practical volumes of DCs from pluripotent stem cells (PSCs) require a large number of PSCs at the start of the differentiation culture. In the current study, we generated mouse proliferating myeloid cells (pMCs) as a source of antigen-presenting cells (APC) using lentivirus-mediated transduction of the c-Myc gene into mouse PSC-derived myeloid cells. The pMCs could propagate almost indefinitely in a cytokine-dependent manner, while retaining their potential to differentiate into functional APCs. After treatment with IL-4 plus GM-CSF, the pMCs showed impaired proliferation and differentiated into immature DC-like cells (pMC-DCs) expressing low levels of major histocompatibility complex (MHC)-I, MHC-II, CD40, CD80 and CD86. In addition, exposure to maturation stimuli induced the production of TNF-α and IL-12p70, and enhanced the expression of MHC-II, CD40 and CD86, which is thus suggestive of typical DC maturation. Similar to bone marrow-derived DCs, they stimulated a primary mixed lymphocyte reaction. Furthermore, the in vivo transfer of pMC-DCs pulsed with H-2Kb-restricted OVA257-264 peptide primed OVA-specific cytotoxic T cells and elicited protection in mice against challenge with OVA-expressing melanoma. Overall, myeloid cells exhibiting cytokine-dependent proliferation and DC-like differentiation may be used to address issues associated with the preparation of DCs.
- Received June 14, 2014.
- Revision received January 18, 2015.
- Accepted January 29, 2015.
- Copyright © 2015, American Association for Cancer Research.