A CD64/FcγRI-mediated mechanism hijacks PD-1 from PD-L1/2 interaction and enhances anti-PD-1 functional recovery of exhausted T cells.
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2023
- doi: 10.3389/fimmu.2023.1213375
- issn: 1664-3224
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info:eu-repo/semantics/altIdentifier/doi/10.3389/fimmu.2023.1213375
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info:eu-repo/semantics/altIdentifier/pmid/37622123
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info:eu-repo/semantics/altIdentifier/eissn/1664-3224
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info:eu-repo/semantics/altIdentifier/urn/urn:nbn:ch:serval-BIB_431B1ABF3E8A4
info:eu-repo/semantics/openAccess , CC BY 4.0 , https://creativecommons.org/licenses/by/4.0/
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Thymus-dependent lymphocytes Thymus-derived cells T lymphocytes Thymus-dependent cellsCiter ce document
V. Joo et al., « A CD64/FcγRI-mediated mechanism hijacks PD-1 from PD-L1/2 interaction and enhances anti-PD-1 functional recovery of exhausted T cells. », Serveur académique Lausannois, ID : 10.3389/fimmu.2023.1213375
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Résumé
Therapeutic monoclonal antibodies (mAb) targeting the immune checkpoint inhibitor programmed cell death protein 1 (PD-1) have achieved considerable clinical success in anti-cancer therapy through relieving T cell exhaustion. Blockade of PD-1 interaction with its ligands PD-L1 and PD-L2 is an important determinant in promoting the functional recovery of exhausted T cells. Here, we show that anti-PD-1 mAbs act through an alternative mechanism leading to the downregulation of PD-1 surface expression on memory CD4 + and CD8 + T cells. PD-1 receptor downregulation is a distinct process from receptor endocytosis and occurs in a CD14 + monocyte dependent manner with the CD64/Fcγ receptor I acting as the primary factor for this T cell extrinsic process. Importantly, downregulation of surface PD-1 strongly enhances antigen-specific functional recovery of exhausted PD-1 + CD8 + T cells. Our study demonstrates a novel mechanism for reducing cell surface levels of PD-1 and limiting the inhibitory targeting by PD-L1/2 and thereby enhancing the efficacy of anti-PD-1 Ab in restoring T cell functionality.