ORIGINAL RESEARCH article
Front. Immunol.
Sec. Microbial Immunology
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1607543
The Gut Microbiota Protein BOC1 Exhibits Immune Checkpoint Inhibitor–Like Activity by Inhibiting Myeloid Derived Suppressor Cells Differentiation
Provisionally accepted
Laureen Bardouillet
María Lucía Orsini Delgado
Caroline MatondoFrancesco StrozziValentine ThomasLaurent Chene
Antonietta Cultrone*- Enterome, Paris, France
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Background: Advancing research in oncology highlights the inversed correlation between antibiotic treatment and the positive outcomes of immune checkpoint inhibitors (ICI) administration, confirming once more the importance of microbiota and microbiota-derived compounds as complementary tools to treat cancer. Among the immune checkpoints, the CD200 cell surface glycoprotein has gained attention for its role in promoting self-tolerance and potentially facilitating tumor growth through interaction with the CD200R1 receptor.We developed a robust AlphaLISA-based screening to identify human gut microbiota derived proteins that may interact with CD200R1 and screened a library of 10966 gut bacterial proteins. Antitumor activity of BOC1 was investigated in vitro by cytokines analysis, Mixed Lymphocyte Reactions and Myeloid-Derived Suppressor Cells (MDSC)-T cells suppression assay. Alpha-Fold modelling was used to predict potential interaction points between BOC1 and CD200R1.We successfully identified BOC1, a protein from the Bacteroides genus, showing better affinity than the natural ligand, CD200, towards CD200R1 receptor. BOC1 induces cytokine secretion by Monocyte-derived Dendritic Cells (MoDC) and enhances CD8 + /CD4 + T cells populations and IFNγ production, highlighting its potent immunostimulatory properties. BOC1 also negatively impacts the differentiation of MDSC maintaining an immature monocytic profile (high CD14 and HLA-DR expression) and restoring T cell proliferation even at low (10 nM) concentration. Mutation of amino acids within the N-terminal region of BOC1 reduces binding to CD200R1, supporting the importance of this region for a possible interaction with CD200R1.The immunostimulatory properties of BOC1 observed in vitro are compatible with an ICI-like behavior of this bacterial protein. Given that nor the CD200 protein, neither an anti-CD200 antibody are able to compete with BOC1 for binding to CD200R1 and, as supported by Alpha-Fold modelling predictions, CD200 and BOC1 might target different regions of CD200R1.
Keywords: Gut Microbiota, immune check-point inhibitor, CD200R1, MDSC, cancer immuno therapy
Received: 07 Apr 2025; Accepted: 24 Jul 2025.
Copyright: © 2025 Bardouillet, Orsini Delgado, Matondo, Strozzi, Thomas, Chene and Cultrone. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Antonietta Cultrone, Enterome, Paris, France
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