T helper-1 lymphocytes induce dendritic cell tumor killing activity by an interferon-γ-dependent mechanism

Dendritic cells (DCs) encompass a heterogeneous population of cells capable of orchestrating innate and adaptive immune responses. The ability of DCs to act as professional antigen presenting cells has been the foundation for the development and utilization of these cells as vaccines in cancer immunotherapy. DCs are also endowed with the non-conventional property of directly killing tumor cells. The current study investigates the regulation of murine DC cytotoxic function by T lymphocytes. We provide evidence that CD4 + Th-1, but not Th-2, Th-17 cells or Treg are capable of inducing DC cytotoxic function. IFN-γ was identified as the major factor responsible for Th-1-induced DC tumoricidal activity. Tumor cell killing mediated by Th-1-activated killer DCs (Th-1 KDCs) was dependent on inducible nitric oxide synthase (iNOS) expression and nitric oxide (NO) production. Importantly, Th-1 KDCs were capable of presenting the acquired antigens from the killed tumor cells to T lymphocytes in vitro or in vivo . These observations open new possibilities for the application of KDCs in cancer immunotherapy.