Formyl peptide receptor-1 (FPR1) represses intestinal oncogenesis
Formyl peptide receptor-1 (FPR1) is a pattern recognition receptor that is mostly expressed by myeloid cells. In patients with colorectal cancer (CRC), a loss-of-function polymorphism (rs867228) in the gene coding for FPR1 has been associated with reduced responses to chemotherapy or chemoradiothera...
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| Language: | English |
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Taylor & Francis Group
2023-12-01
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| Series: | OncoImmunology |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/2162402X.2023.2237354 |
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| author | Julie Le Naour Léa Montégut Yuhong Pan Sarah Adriana Scuderi Pierre Cordier Adrien Joseph Allan Sauvat Valerio Iebba Juliette Paillet Gladys Ferrere Ludivine Brechard Claire Mulot Grégory Dubourg Laurence Zitvogel Jonathan G. Pol Erika Vacchelli Pierre-Laurent Puig Guido Kroemer |
| author_facet | Julie Le Naour Léa Montégut Yuhong Pan Sarah Adriana Scuderi Pierre Cordier Adrien Joseph Allan Sauvat Valerio Iebba Juliette Paillet Gladys Ferrere Ludivine Brechard Claire Mulot Grégory Dubourg Laurence Zitvogel Jonathan G. Pol Erika Vacchelli Pierre-Laurent Puig Guido Kroemer |
| author_sort | Julie Le Naour |
| collection | DOAJ |
| description | Formyl peptide receptor-1 (FPR1) is a pattern recognition receptor that is mostly expressed by myeloid cells. In patients with colorectal cancer (CRC), a loss-of-function polymorphism (rs867228) in the gene coding for FPR1 has been associated with reduced responses to chemotherapy or chemoradiotherapy. Moreover, rs867228 is associated with accelerated esophageal and colorectal carcinogenesis. Here, we show that dendritic cells from Fpr1−/− mice exhibit reduced migration in response to chemotherapy-treated CRC cells. Moreover, Fpr1−/− mice are particularly susceptible to chronic ulcerative colitis and colorectal oncogenesis induced by the mutagen azoxymethane followed by oral dextran sodium sulfate, a detergent that induces colitis. These experiments were performed after initial co-housing of Fpr1−/− mice and wild-type controls, precluding major Fpr1-driven differences in the microbiota. Pharmacological inhibition of Fpr1 by cyclosporin H also tended to increase intestinal oncogenesis in mice bearing the ApcMin mutation, and this effect was reversed by the anti-inflammatory drug sulindac. We conclude that defective FPR1 signaling favors intestinal tumorigenesis through the modulation of the innate inflammatory/immune response. |
| format | Article |
| id | doaj-art-93d49cebbe9e4c6cb76a095b6b9395fa |
| institution | DOAJ |
| issn | 2162-402X |
| language | English |
| publishDate | 2023-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | OncoImmunology |
| spelling | doaj-art-93d49cebbe9e4c6cb76a095b6b9395fa2025-08-20T02:50:44ZengTaylor & Francis GroupOncoImmunology2162-402X2023-12-0112110.1080/2162402X.2023.2237354Formyl peptide receptor-1 (FPR1) represses intestinal oncogenesisJulie Le Naour0Léa Montégut1Yuhong Pan2Sarah Adriana Scuderi3Pierre Cordier4Adrien Joseph5Allan Sauvat6Valerio Iebba7Juliette Paillet8Gladys Ferrere9Ludivine Brechard10Claire Mulot11Grégory Dubourg12Laurence Zitvogel13Jonathan G. Pol14Erika Vacchelli15Pierre-Laurent Puig16Guido Kroemer17Centre de Recherche des Cordeliers, Equipe Labellisée Par la Ligue Contre le Cancer, Université Paris Cité, Sorbonne Université, Inserm U1138, Institut Universitaire de France, Paris, FranceCentre de Recherche des Cordeliers, Equipe Labellisée Par la Ligue Contre le Cancer, Université Paris Cité, Sorbonne Université, Inserm U1138, Institut Universitaire de France, Paris, FranceCentre de Recherche des Cordeliers, Equipe Labellisée Par la Ligue Contre le Cancer, Université Paris Cité, Sorbonne Université, Inserm U1138, Institut Universitaire de France, Paris, FranceCentre de Recherche des Cordeliers, Equipe Labellisée Par la Ligue Contre le Cancer, Université Paris Cité, Sorbonne Université, Inserm U1138, Institut Universitaire de France, Paris, FranceLaboratory of Proliferation, Stress and Liver Physiopathology, Centre de Recherche des Cordeliers, INSERM, Sorbonne Université, Université Paris Cité, Paris, FranceCentre de Recherche des Cordeliers, Equipe Labellisée Par la Ligue Contre le Cancer, Université Paris Cité, Sorbonne Université, Inserm U1138, Institut Universitaire de France, Paris, FranceCentre de Recherche des Cordeliers, Equipe Labellisée Par la Ligue Contre le Cancer, Université Paris Cité, Sorbonne Université, Inserm U1138, Institut Universitaire de France, Paris, FranceDepartment of Medical, Surgical and Health Sciences, University of Trieste, Trieste, ItalyCentre de Recherche des Cordeliers, Equipe Labellisée Par la Ligue Contre le Cancer, Université Paris Cité, Sorbonne Université, Inserm U1138, Institut Universitaire de France, Paris, FranceInstitut National de la Santé Et de la Recherche Medicale (INSERM) U1015 and Equipe Labellisée–Ligue Nationale Contre le Cancer, Villejuif, FranceAix Marseille Univ, IRD, AP-HM, MEPHI, IHU Méditerranée Infection, Marseille, FranceCentre de Recherche des Cordeliers, Equipe Labélisée Ligue Contre le Cancer, Sorbonne Université, Université Paris Cité, INSERM, Paris, FranceAix Marseille Univ, IRD, AP-HM, MEPHI, IHU Méditerranée Infection, Marseille, FranceFaculty of Medicine Kremlin Bicêtre, Université Paris Saclay, Le Kremlin Bicêtre, FranceCentre de Recherche des Cordeliers, Equipe Labellisée Par la Ligue Contre le Cancer, Université Paris Cité, Sorbonne Université, Inserm U1138, Institut Universitaire de France, Paris, FranceCentre de Recherche des Cordeliers, Equipe Labellisée Par la Ligue Contre le Cancer, Université Paris Cité, Sorbonne Université, Inserm U1138, Institut Universitaire de France, Paris, FranceCentre de Recherche des Cordeliers, Equipe Labélisée Ligue Contre le Cancer, Sorbonne Université, Université Paris Cité, INSERM, Paris, FranceCentre de Recherche des Cordeliers, Equipe Labellisée Par la Ligue Contre le Cancer, Université Paris Cité, Sorbonne Université, Inserm U1138, Institut Universitaire de France, Paris, FranceFormyl peptide receptor-1 (FPR1) is a pattern recognition receptor that is mostly expressed by myeloid cells. In patients with colorectal cancer (CRC), a loss-of-function polymorphism (rs867228) in the gene coding for FPR1 has been associated with reduced responses to chemotherapy or chemoradiotherapy. Moreover, rs867228 is associated with accelerated esophageal and colorectal carcinogenesis. Here, we show that dendritic cells from Fpr1−/− mice exhibit reduced migration in response to chemotherapy-treated CRC cells. Moreover, Fpr1−/− mice are particularly susceptible to chronic ulcerative colitis and colorectal oncogenesis induced by the mutagen azoxymethane followed by oral dextran sodium sulfate, a detergent that induces colitis. These experiments were performed after initial co-housing of Fpr1−/− mice and wild-type controls, precluding major Fpr1-driven differences in the microbiota. Pharmacological inhibition of Fpr1 by cyclosporin H also tended to increase intestinal oncogenesis in mice bearing the ApcMin mutation, and this effect was reversed by the anti-inflammatory drug sulindac. We conclude that defective FPR1 signaling favors intestinal tumorigenesis through the modulation of the innate inflammatory/immune response.https://www.tandfonline.com/doi/10.1080/2162402X.2023.2237354Bone marrow-derived dendritic cellschemotaxisimmunogenic chemotherapyimmunosurveillancetumor microenvironment |
| spellingShingle | Julie Le Naour Léa Montégut Yuhong Pan Sarah Adriana Scuderi Pierre Cordier Adrien Joseph Allan Sauvat Valerio Iebba Juliette Paillet Gladys Ferrere Ludivine Brechard Claire Mulot Grégory Dubourg Laurence Zitvogel Jonathan G. Pol Erika Vacchelli Pierre-Laurent Puig Guido Kroemer Formyl peptide receptor-1 (FPR1) represses intestinal oncogenesis OncoImmunology Bone marrow-derived dendritic cells chemotaxis immunogenic chemotherapy immunosurveillance tumor microenvironment |
| title | Formyl peptide receptor-1 (FPR1) represses intestinal oncogenesis |
| title_full | Formyl peptide receptor-1 (FPR1) represses intestinal oncogenesis |
| title_fullStr | Formyl peptide receptor-1 (FPR1) represses intestinal oncogenesis |
| title_full_unstemmed | Formyl peptide receptor-1 (FPR1) represses intestinal oncogenesis |
| title_short | Formyl peptide receptor-1 (FPR1) represses intestinal oncogenesis |
| title_sort | formyl peptide receptor 1 fpr1 represses intestinal oncogenesis |
| topic | Bone marrow-derived dendritic cells chemotaxis immunogenic chemotherapy immunosurveillance tumor microenvironment |
| url | https://www.tandfonline.com/doi/10.1080/2162402X.2023.2237354 |
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