Tickling APCsThe p84/p110 complex of PI3K regulates NOX2 assembly and cross-presentation of immune complexes

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Adiko, Aimé Cézaire | Bens, Marcelle | Tandon, Naman | Benadda, Samira | Boedec, Erwan | Pellé, Olivier | El-Benna, Jamel | Monteiro, Renato | Laffargue, Muriel | Stephens, Len | Guermonprez, Pierre | Saveanu, Loredana

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International audience. Antibody-mediated cross-presentation is known to elicit strong CD8+ T cell responses, particularly relevant in cancer therapy. Anti-tumor antibodies are known to rapidly kill cancer cells by antibody-dependent cellular cytotoxicity (ADCC), but the long-term immune control of tumors is based on induction of CD8+ T cell response, which relays on anti-tumor antibody-mediated cross-presentation. The molecular mechanisms by which this pathway of cross-presentation allows to poor cross-presenting cells, such as type 2 dendritic cells (DCs) and monocyte-derived DCs (moDCs), to efficiently cross present are not well understood. We demonstrated that enzymatic activity of p84/p110g complex of PI3Kg regulates the assembly of NADPH oxidase NOX2 and ROS production in type 2 DCs from mouse spleen and murine bone marrow derived DCs, enhancing thus the cross-presentation of immune complexes by these cells. Our results suggest that the association between anti-tumor monoclonal antibodies and PI3Kg inhibitors might block the antibody-mediated cross-presentation of tumor antigens and should be avoided in clinical therapy of cancers.

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