TLR7-Induced Mitochondrial Reactive Oxygen Species Production in Monocyte-derived Dendritic Cells Drives IL-12-Dependent NK Cell Activation and Enhances Antitumor Immunity.
| Autor: | Paladhi A; Cellular Immunology Laboratory, Department of Zoology, University of Burdwan, Bardhaman, India., Daripa S; Cellular Immunology Laboratory, Department of Zoology, University of Burdwan, Bardhaman, India., Nath A; ICMR-DHR-VRDL, Burdwan Medical College and Hospital, Bardhaman, India., Hira SK; Cellular Immunology Laboratory, Department of Zoology, University of Burdwan, Bardhaman, India. |
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| Jazyk: | angličtina |
| Zdroj: | Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2024 Oct 15; Vol. 213 (8), pp. 1255-1263. |
| DOI: | 10.4049/jimmunol.2400340 |
| Abstrakt: | Dendritic cell (DC)-based vaccines are promising immunotherapies for cancer. Although DC-based therapies are known to activate tumor-specific T cells, the interplay between DCs and NK cells in this setting is not fully understood. In this study, we demonstrated a novel TLR7/ mitochondrial reactive oxygen species (mROS)/IL-12 axis that drives potent NK cell responses against tumors. We showed that TLR7 activation by imiquimod in peripheral blood monocyte-derived CD11c+ DCs triggered mROS production, leading to enhanced IL-12 secretion and subsequent NK cell activation, as evidenced by increased IFN-γ production and tumor cell cytotoxicity. Notably, mROS neutralization abrogates NK cell-mediated tumor cell lysis, and TLR7-mediated DC activation of NK cells occurs independently of MyD88, suggesting involvement of the noncanonical NF-κB pathway. Our findings provide a rationale for targeting the TLR7/mROS/IL-12 axis to enhance the efficacy of DC-based cancer immunotherapy. (Copyright © 2024 by The American Association of Immunologists, Inc.) |
| Databáze: | MEDLINE |
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