Dendritic cells trigger tumor cell death by a nitric oxide-dependent mechanism
Dendritic cells trigger tumor cell death by a nitric oxide-dependent mechanism
Dendritic cells (DCs) are well known for their capacity to induce adaptive antitumor immune response through Ag presentation and tumor-specific T cell activation. Recent findings reveal that besides this role, DCs may display additional antitumor effects. In this study, we provide evidence that LPS- or IFN-gamma-activated rat bone marrow-derived dendritic cells (BMDCs) display killing properties against tumor cells. These cytotoxic BMDCs exhibit a mature DC phenotype, produce high amounts of IL-12, IL-6, and TNF-alpha, and retain their phagocytic properties. BMDC-mediated tumor cell killing requires cell-cell contact and depends on NO production, but not on perforin/granzyme or on death receptors. Furthermore, dead tumor cells do not exhibit characteristics of apoptosis. Thus, intratumoral LPS injections induce an increase of inducible NO synthase expression in tumor-infiltrating DCs associated with a significant arrest of tumor growth. Altogether, these results suggest that LPS-activated BMDCs represent powerful tumoricidal cells which enforce their potential as anticancer cellular vaccines.
812-818
Nicolas, Alexandra
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Cathelin, Dominique
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Larmonier, Nicolas
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Fraszczak, Jennifer
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Puig, Pierre-Emmanuel
58273dd3-42e6-4aed-8b96-d5763042fcfe
Bouchot, André
2a41fb59-f87b-427e-b4ac-c3eb628be7d9
Bateman, Andrew
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Solary, Eric
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Bonnotte, Bernard
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15 July 2007
Nicolas, Alexandra
b9379cb3-f5e2-41e6-b968-7ac5d6e3c571
Cathelin, Dominique
04b06d66-450d-44da-844a-b5ff1c2c005c
Larmonier, Nicolas
34838c5e-2252-4fb7-bb46-40a2c0fd7bec
Fraszczak, Jennifer
45696db2-bf80-489c-b397-d41722482b45
Puig, Pierre-Emmanuel
58273dd3-42e6-4aed-8b96-d5763042fcfe
Bouchot, André
2a41fb59-f87b-427e-b4ac-c3eb628be7d9
Bateman, Andrew
a851558d-8b9b-4020-b148-a239c2b26815
Solary, Eric
24be0113-0d6f-49bd-94e6-54de6080eb2d
Bonnotte, Bernard
4c48748d-32fa-4ee3-88d1-7e69dfa9259a
Nicolas, Alexandra, Cathelin, Dominique, Larmonier, Nicolas, Fraszczak, Jennifer, Puig, Pierre-Emmanuel, Bouchot, André, Bateman, Andrew, Solary, Eric and Bonnotte, Bernard
(2007)
Dendritic cells trigger tumor cell death by a nitric oxide-dependent mechanism.
Journal of Immunology, 179 (2), .
Abstract
Dendritic cells (DCs) are well known for their capacity to induce adaptive antitumor immune response through Ag presentation and tumor-specific T cell activation. Recent findings reveal that besides this role, DCs may display additional antitumor effects. In this study, we provide evidence that LPS- or IFN-gamma-activated rat bone marrow-derived dendritic cells (BMDCs) display killing properties against tumor cells. These cytotoxic BMDCs exhibit a mature DC phenotype, produce high amounts of IL-12, IL-6, and TNF-alpha, and retain their phagocytic properties. BMDC-mediated tumor cell killing requires cell-cell contact and depends on NO production, but not on perforin/granzyme or on death receptors. Furthermore, dead tumor cells do not exhibit characteristics of apoptosis. Thus, intratumoral LPS injections induce an increase of inducible NO synthase expression in tumor-infiltrating DCs associated with a significant arrest of tumor growth. Altogether, these results suggest that LPS-activated BMDCs represent powerful tumoricidal cells which enforce their potential as anticancer cellular vaccines.
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Published date: 15 July 2007
Identifiers
Local EPrints ID: 47610
URI: http://eprints.soton.ac.uk/id/eprint/47610
ISSN: 0022-1767
PURE UUID: 70ec667e-f913-41a6-a996-5a613e13dc5e
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Date deposited: 06 Aug 2007
Last modified: 15 Mar 2024 09:34
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Contributors
Author:
Alexandra Nicolas
Author:
Dominique Cathelin
Author:
Nicolas Larmonier
Author:
Jennifer Fraszczak
Author:
Pierre-Emmanuel Puig
Author:
André Bouchot
Author:
Andrew Bateman
Author:
Eric Solary
Author:
Bernard Bonnotte
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