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

• DOI: 10.1016/j.molimm.2022.05.063
• Publication Date: 2022-10-13T16:41:26Z
• Authors: Aimé Cézaire Adiko; Marcelle Bens; Naman Tandon; Samira Benadda; Erwan Boedec; Olivier Pellé; Jamel El-Benna; Renato Monteiro; Muriel Laffargue; Len Stephens; Pierre Guermonprez; Loredana Saveanu
• Keywords: Cross-Presentation; Plasmacytoid dendritic cell

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.