Despite weak antigen (Ag) uptake by monocytes, Huang et al. show that protein- or MHC-I-restricted-peptide-Ag- loaded undifferentiated monocytes injected IV induced stronger antitumor activity than DC-, protein/adjuvant-, or tumor cell- based vaccines in two aggressive murine tumor models. Cell contact-dependent connexin 43-containing gap junction formation, but not phago- or trogo- cytosis, was required for Ag transfer from monocytes to splenic white pulp (but not lymph node) CD8+ cDCs, which then cross-primed naive CD8+ T cells to become potent cytolytic cells. DCs were also required for monocyte Ag activation of human T cells in vitro.

Contributed by Paula Hochman

Efficacy of dendritic cell (DC) cancer vaccines is classically thought to depend on their antigen-presenting cell (APC) activity. Studies show, however, that DC vaccine priming of cytotoxic T lymphocytes (CTL) requires the activity of endogenous DC, suggesting that exogenous DC stimulate anti-tumor immunity by transferring antigen (Ag) to endogenous DC. Such Ag transfer functions are most commonly ascribed to monocytes, implying that undifferentiated monocytes would function equally well as a vaccine modality and need not be differentiated to DC to be effective. Here, we used several murine cancer models to test the anti-tumor efficacy of undifferentiated monocytes loaded with protein or peptide Ag. Intravenously injected monocytes displayed anti-tumor activity superior to DC vaccines in several cancer models, including aggressive intracranial glioblastoma. Ag-loaded monocytes induced robust CTL responses via Ag transfer to splenic CD8+ DC in a manner independent of monocyte APC activity. Ag transfer required cell-cell contact and the formation of connexin 43-containing gap junctions between monocytes and DC. These findings demonstrate the existence of an efficient gap junction-mediated Ag transfer pathway between monocytes and CD8+ DC and suggest that administration of tumor Ag-loaded undifferentiated monocytes may serve as a simple and efficacious immunotherapy for the treatment of human cancers.

Author Info: (1) (2) (3) (4) (5) (6) (7) (8) (9) (10) (11) (12)

Author Info: (1) (2) (3) (4) (5) (6) (7) (8) (9) (10) (11) (12)