Cytokine-armed dendritic cell progenitors for antigen-agnostic cancer immunotherapy

Nat Cancer. 2024 Feb;5(2):240-261. doi: 10.1038/s43018-023-00668-y. Epub 2023 Nov 23.


Dendritic cells (DCs) are antigen-presenting myeloid cells that regulate T cell activation, trafficking and function. Monocyte-derived DCs pulsed with tumor antigens have been tested extensively for therapeutic vaccination in cancer, with mixed clinical results. Here, we present a cell-therapy platform based on mouse or human DC progenitors (DCPs) engineered to produce two immunostimulatory cytokines, IL-12 and FLT3L. Cytokine-armed DCPs differentiated into conventional type-I DCs (cDC1) and suppressed tumor growth, including melanoma and autochthonous liver models, without the need for antigen loading or myeloablative host conditioning. Tumor response involved synergy between IL-12 and FLT3L and was associated with natural killer and T cell infiltration and activation, M1-like macrophage programming and ischemic tumor necrosis. Antitumor immunity was dependent on endogenous cDC1 expansion and interferon-γ signaling but did not require CD8+ T cell cytotoxicity. Cytokine-armed DCPs synergized effectively with anti-GD2 chimeric-antigen receptor (CAR) T cells in eradicating intracranial gliomas in mice, illustrating their potential in combination therapies.

MeSH terms

  • Animals
  • Cytokines*
  • Dendritic Cells
  • Humans
  • Immunotherapy
  • Interleukin-12
  • Mice
  • Neoplasms* / therapy


  • Cytokines
  • Interleukin-12