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 APCs has been the foundation for the development and use of these cells as vaccines in cancer immunotherapy. DCs are also endowed with the nonconventional 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 regulatory T cells, 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 was dependent on inducible NO synthase expression and NO production. Importantly, Th-1–activated killer DCs were capable of presenting the acquired Ags from the killed tumor cells to T lymphocytes in vitro or in vivo. These observations offer new possibilities for the application of killer DCs in cancer immunotherapy.
This work was supported by National Institutes of Health Grant R01 CA104926 (to E.K. and N.L.), Cancer Biology Training Grant T32CA009213 (to S.C.), Arizona Cancer Center Support Grant CA023074 (to E.K. and N.L.), Tee Up for Tots, and PANDA Funds (to E.K. and N.L.).
The online version of this article contains supplemental material.
- Received June 22, 2011.
- Accepted October 12, 2011.
- Copyright © 2011 by The American Association of Immunologists, Inc.