Antigen-loaded monocyte administration induces potent therapeutic antitumor T cell responses
- 3 February 2020
- journal article
- research article
- Published by American Society for Clinical Investigation in JCI Insight
- Vol. 130 (2), 774-788
- https://doi.org/10.1172/JCI128267
Abstract
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 (CTLs) requires the activity of endogenous DCs, suggesting that exogenous DCs stimulate antitumor immunity by transferring antigens (Ags) to endogenous DCs. 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 DCs to be effective. Here, we used several murine cancer models to test the antitumor efficacy of undifferentiated monocytes loaded with protein or peptide Ag. Intravenously injected monocytes displayed antitumor 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(+) DCs 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 Xs. These findings demonstrate the existence of an efficient gap junction-mediated Ag transfer pathway between monocytes and CD8(+) DCs and suggest that administration of tumor Ag-loaded undifferentiated monocytes may serve as a simple and efficacious immunotherapy for the treatment of human cancers.Funding Information
- National Cancer Center (P50 CA 190991)
- Duke University School of Medicine (Duke Chancellor’s Program Project Accelerator Award)
This publication has 80 references indexed in Scilit:
- Migratory properties of pulmonary dendritic cells are determined by their developmental lineageMucosal Immunology, 2013
- Myelosuppressive Conditioning Using Busulfan Enables Bone Marrow Cell Accumulation in the Spinal Cord of a Mouse Model of Amyotrophic Lateral SclerosisPLOS ONE, 2013
- Cancer immunotherapy via dendritic cellsNature Reviews Cancer, 2012
- Cross-dressed dendritic cells drive memory CD8+ T-cell activation after viral infectionNature, 2011
- Cross-dressers turn on T cellsNature, 2011
- Microbial Stimulation Fully Differentiates Monocytes to DC-SIGN/CD209+ Dendritic Cells for Immune T Cell AreasCell, 2010
- CD205 (DEC-205): A recognition receptor for apoptotic and necrotic selfMolecular Immunology, 2009
- Blood-derived inflammatory dendritic cells in lymph nodes stimulate acute T helper type 1 immune responsesNature Immunology, 2009
- Antigen presentation by monocytes and monocyte-derived cellsCurrent Opinion in Immunology, 2008
- Monocyte and macrophage heterogeneityNature Reviews Immunology, 2005