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Article ; Online: Large-scale analysis of cell-cell communication reveals angiogenin-dependent tumor progression in clear cell renal cell carcinoma.

Massenet-Regad, Lucile / Poirot, Justine / Jackson, Margaret / Hoffmann, Caroline / Amblard, Elise / Onodi, Fanny / Bouhidel, Fatiha / Djouadou, Malika / Ouzaid, Idir / Xylinas, Evanguelos / Medvedovic, Jasna / Soumelis, Vassili

iScience

2023 Volume 26, Issue 12, Page(s) 108367

Abstract: Cellular crosstalk in the tumor microenvironment (TME) is still largely uncharacterized, while it plays an essential role in shaping immunosuppression or anti-tumor response. Large-scale analyses are needed to better decipher cell-cell communication in ... ...

Abstract	Cellular crosstalk in the tumor microenvironment (TME) is still largely uncharacterized, while it plays an essential role in shaping immunosuppression or anti-tumor response. Large-scale analyses are needed to better decipher cell-cell communication in cancer. In this work, we used original and publicly available single-cell RNA sequencing (scRNAseq) data to characterize in-depth the communication networks in human clear cell renal cell carcinoma (ccRCC). We identified 50 putative communication channels specifically used by cancer cells to interact with other cells, including two novel angiogenin-mediated interactions. Expression of angiogenin and its receptors was validated at the protein level in primary ccRCC. Mechanistically, angiogenin enhanced ccRCC cell line proliferation and down-regulated secretion of IL-6, IL-8, and MCP-1 proinflammatory molecules. This study provides novel biological insights into molecular mechanisms of ccRCC, and suggests angiogenin and its receptors as potential therapeutic targets in clear cell renal cancer.
Language	English
Publishing date	2023-10-31
Publishing country	United States
Document type	Journal Article
ISSN	2589-0042
ISSN (online)	2589-0042
DOI	10.1016/j.isci.2023.108367
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Article ; Online: Large-scale analysis of cell-cell communication reveals angiogenin-dependent tumor progression in clear cell renal cell carcinoma

Lucile Massenet-Regad / Justine Poirot / Margaret Jackson / Caroline Hoffmann / Elise Amblard / Fanny Onodi / Fatiha Bouhidel / Malika Djouadou / Idir Ouzaid / Evanguelos Xylinas / Jasna Medvedovic / Vassili Soumelis

iScience, Vol 26, Iss 12, Pp 108367- (2023)

2023

Abstract: Summary: Cellular crosstalk in the tumor microenvironment (TME) is still largely uncharacterized, while it plays an essential role in shaping immunosuppression or anti-tumor response. Large-scale analyses are needed to better decipher cell-cell ... ...

Abstract	Summary: Cellular crosstalk in the tumor microenvironment (TME) is still largely uncharacterized, while it plays an essential role in shaping immunosuppression or anti-tumor response. Large-scale analyses are needed to better decipher cell-cell communication in cancer. In this work, we used original and publicly available single-cell RNA sequencing (scRNAseq) data to characterize in-depth the communication networks in human clear cell renal cell carcinoma (ccRCC). We identified 50 putative communication channels specifically used by cancer cells to interact with other cells, including two novel angiogenin-mediated interactions. Expression of angiogenin and its receptors was validated at the protein level in primary ccRCC. Mechanistically, angiogenin enhanced ccRCC cell line proliferation and down-regulated secretion of IL-6, IL-8, and MCP-1 proinflammatory molecules. This study provides novel biological insights into molecular mechanisms of ccRCC, and suggests angiogenin and its receptors as potential therapeutic targets in clear cell renal cancer.
Keywords	Microenvironment ; Cancer ; Transcriptomics ; Science ; Q
Language	English
Publishing date	2023-12-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Paraneoplastic pemphigus uncovers distinct clinical and biological phenotypes of western unicentric Castleman disease.

Dieudonné, Yannick / Silvestrini, Marc-Antoine / Dossier, Antoine / Meignin, Véronique / Jouenne, Fanélie / Mahévas, Thibault / Bouaziz, Jean-David / Jackson, Margaret A / Mordant, Pierre / Poirot, Justine / Onodi, Fanny / Calvani, Julien / Hourseau, Muriel / Evrard, Diane / Berisha, Mirlinda / Perrin, François / Danel, Claire / Borie, Raphael / Galicier, Lionel /

Mourah, Samia / Bengoufa, Djaouida / Oksenhendler, Eric / Grootenboer-Mignot, Sabine / Boutboul, David

British journal of haematology

2023 Volume 202, Issue 2, Page(s) 267–278

Abstract: Unicentric Castleman disease (UCD) is a lymphoproliferative disease of unknown cause. Paraneoplastic pemphigus (PNP) is a major complication shown to be associated with a poor prognosis, with particular severity in patients with bronchiolitis obliterans ( ...

Abstract	Unicentric Castleman disease (UCD) is a lymphoproliferative disease of unknown cause. Paraneoplastic pemphigus (PNP) is a major complication shown to be associated with a poor prognosis, with particular severity in patients with bronchiolitis obliterans (BO). This study describes the clinical and biological characteristics of UCD-PNP patients in a large Western cohort. A total of 148 patients diagnosed with UCD were identified, including 14 patients with a defined PNP. PNP was significantly associated with myasthenia gravis (MG) and FDC sarcoma during follow-up (FDCS). PNP was also significantly associated with reduced survival. These data, together with a multivariate analysis by principal components, led to the identification of UCD-PNP as a group at risk of MG, FDCS and death. PDGFRB sequencing performed on UCD lesions from six patients found the gain-of-function p.N666S variant in two. Interestingly, both patients had hyaline-vascular UCD subtype, were in the UCD-PNP subgroup and had FDCS. Sera from 25 UCD-PNP patients and 6 PNP patients without UCD were tested for PNP-associated autoantibodies. Sera from UCD-PNP patients had a strong reactivity against the N-terminal domain of recombinant periplakin (rPPL, 82%) and showed reactivity against at least two domains of rPPL. These features were not found in patients with UCD alone or in the PNP group without UCD. These data indicate that UCD-PNP patients belong to a subgroup sharing strong clinical and biological identity that might help to decipher the different dynamics of UCD natural history.
MeSH term(s)	Humans ; Pemphigus/diagnosis ; Pemphigus/etiology ; Castleman Disease/pathology ; Autoantibodies ; Myasthenia Gravis/diagnosis ; Paraneoplastic Syndromes/etiology ; Paraneoplastic Syndromes/diagnosis
Chemical Substances	Autoantibodies
Language	English
Publishing date	2023-05-23
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80077-6
ISSN	1365-2141 ; 0007-1048
ISSN (online)	1365-2141
ISSN	0007-1048
DOI	10.1111/bjh.18847
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Article: Temporary Reduction of Membrane CD4 with the Antioxidant MnTBAP Is Sufficient to Prevent Immune Responses Induced by Gene Transfer.

Da Rocha, Sylvie / Bigot, Jérémy / Onodi, Fanny / Cosette, Jérémie / Corre, Guillaume / Poupiot, Jérôme / Fenard, David / Gjata, Bernard / Galy, Anne / Neildez-Nguyen, Thi My Anh

Molecular therapy. Methods & clinical development

2019 Volume 14, Page(s) 285–299

Abstract: Unexpectedly, the synthetic antioxidant MnTBAP was found to cause a rapid and reversible downregulation of CD4 on T ... ...

Abstract	Unexpectedly, the synthetic antioxidant MnTBAP was found to cause a rapid and reversible downregulation of CD4 on T cells
Language	English
Publishing date	2019-07-23
Publishing country	United States
Document type	Journal Article
ZDB-ID	2872938-9
ISSN	2329-0501 ; 2329-0501
ISSN (online)	2329-0501
ISSN	2329-0501
DOI	10.1016/j.omtm.2019.06.011
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Article: SARS-CoV-2 induces human plasmacytoid pre-dendritic cell diversification via UNC93B and IRAK4.

Onodi, Fanny / Bonnet-Madin, Lucie / Meertens, Laurent / Karpf, Léa / Poirot, Justine / Zhang, Shen-Ying / Picard, Capucine / Puel, Anne / Jouanguy, Emmanuelle / Zhang, Qian / Le Goff, Jérôme / Molina, Jean-Michel / Delaugerre, Constance / Casanova, Jean-Laurent / Amara, Ali / Soumelis, Vassili

bioRxiv : the preprint server for biology

2021

Abstract: Several studies have analyzed antiviral immune pathways in late-stage severe COVID-19. However, the initial steps of SARS-CoV-2 antiviral immunity are poorly understood. Here, we have isolated primary SARS-CoV-2 viral strains, and studied their ... ...

Abstract	Several studies have analyzed antiviral immune pathways in late-stage severe COVID-19. However, the initial steps of SARS-CoV-2 antiviral immunity are poorly understood. Here, we have isolated primary SARS-CoV-2 viral strains, and studied their interaction with human plasmacytoid pre-dendritic cells (pDC), a key player in antiviral immunity. We show that pDC are not productively infected by SARS-CoV-2. However, they efficiently diversified into activated P1-, P2-, and P3-pDC effector subsets in response to viral stimulation. They expressed CD80, CD86, CCR7, and OX40 ligand at levels similar to influenza virus-induced activation. They rapidly produced high levels of interferon-α, interferon-λ1, IL-6, IP-10, and IL-8. All major aspects of SARS-CoV-2-induced pDC activation were inhibited by hydroxychloroquine. Mechanistically, SARS-CoV-2-induced pDC activation critically depended on IRAK4 and UNC93B1, as established using pDC from genetically deficient patients. Overall, our data indicate that human pDC are efficiently activated by SARS-CoV-2 particles and may thus contribute to type I IFN-dependent immunity against SARS-CoV-2 infection.
Language	English
Publishing date	2021-01-08
Publishing country	United States
Document type	Preprint
DOI	10.1101/2020.07.10.197343
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Article ; Online: SARS-CoV-2 induces human plasmacytoid predendritic cell diversification via UNC93B and IRAK4.

The Journal of experimental medicine

2021 Volume 218, Issue 4

Abstract: Several studies have analyzed antiviral immune pathways in late-stage severe COVID-19. However, the initial steps of SARS-CoV-2 antiviral immunity are poorly understood. Here we have isolated primary SARS-CoV-2 viral strains and studied their interaction ...

Abstract	Several studies have analyzed antiviral immune pathways in late-stage severe COVID-19. However, the initial steps of SARS-CoV-2 antiviral immunity are poorly understood. Here we have isolated primary SARS-CoV-2 viral strains and studied their interaction with human plasmacytoid predendritic cells (pDCs), a key player in antiviral immunity. We show that pDCs are not productively infected by SARS-CoV-2. However, they efficiently diversified into activated P1-, P2-, and P3-pDC effector subsets in response to viral stimulation. They expressed CD80, CD86, CCR7, and OX40 ligand at levels similar to influenza virus-induced activation. They rapidly produced high levels of interferon-α, interferon-λ1, IL-6, IP-10, and IL-8. All major aspects of SARS-CoV-2-induced pDC activation were inhibited by hydroxychloroquine. Mechanistically, SARS-CoV-2-induced pDC activation critically depended on IRAK4 and UNC93B1, as established using pDC from genetically deficient patients. Overall, our data indicate that human pDC are efficiently activated by SARS-CoV-2 particles and may thus contribute to type I IFN-dependent immunity against SARS-CoV-2 infection.
MeSH term(s)	Biomarkers ; COVID-19/drug therapy ; COVID-19/immunology ; COVID-19/metabolism ; COVID-19/virology ; Cell Plasticity/immunology ; Cytokines/metabolism ; Dendritic Cells/immunology ; Dendritic Cells/metabolism ; Dendritic Cells/virology ; Host-Pathogen Interactions/immunology ; Humans ; Hydroxychloroquine/pharmacology ; Hydroxychloroquine/therapeutic use ; Immunomodulation ; Immunophenotyping ; Inflammation Mediators/metabolism ; Interferon Type I/metabolism ; Interferons/metabolism ; Interleukin-1 Receptor-Associated Kinases/metabolism ; Membrane Transport Proteins/metabolism ; SARS-CoV-2/immunology
Chemical Substances	Biomarkers ; Cytokines ; Inflammation Mediators ; Interferon Type I ; Membrane Transport Proteins ; UNC93B1 protein, human ; interferon type III ; Hydroxychloroquine (4QWG6N8QKH) ; Interferons (9008-11-1) ; IRAK4 protein, human (EC 2.7.11.1) ; Interleukin-1 Receptor-Associated Kinases (EC 2.7.11.1)
Language	English
Publishing date	2021-02-19
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	218343-2
ISSN	1540-9538 ; 0022-1007
ISSN (online)	1540-9538
ISSN	0022-1007
DOI	10.1084/jem.20201387
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Article ; Online: SARS-CoV-2 induces activation and diversification of human plasmacytoid pre-dendritic cells

Onodi, Fanny / Bonnet-Madin, Lucie / Karpf, Léa / Meertens, Laurent / Poirot, Justine / Legoff, Jérome / Delaugerre, Constance / Amara, Ali / Soumelis, Vassili

bioRxiv

Abstract: Several studies have analyzed antiviral immune pathways in severe COVID-19 patients. However, the initial steps of antiviral immunity are not known. Here, we have studied the interaction of isolated primary SARS-CoV-2 viral strains with human ... ...

Abstract	Several studies have analyzed antiviral immune pathways in severe COVID-19 patients. However, the initial steps of antiviral immunity are not known. Here, we have studied the interaction of isolated primary SARS-CoV-2 viral strains with human plasmacytoid pre-dendritic cells (pDC), a key player in antiviral immunity. We show that pDC are not permissive to SARS-CoV-2 infection. However, they efficiently diversified into activated P1-, P2-, and P3-pDC effector subsets in response to viral stimulation. They expressed checkpoint molecules at levels similar to influenza virus-induced activation. They rapidly produced high levels of interferon-α, interferon-λ1, IL-6, IP-10, and IL-8. Importantly, all major aspects of SARS-CoV-2-induced pDC activation were inhibited by hydroxychloroquine, including P2- and P3-pDC differentiation, the expression of maturation markers, and the production of interferon-α and inflammatory cytokines. Our results indicate that pDC may represent a major player in the first line of defense against SARS-CoV-2 infection, and call for caution in the use of hydroxychloroquine in the early treatment of the disease.
Keywords	covid19
Publisher	BioRxiv; WHO
Document type	Article ; Online
DOI	10.1101/2020.07.10.197343
Database	COVID19

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Article ; Online: Single Cell Dynamics Causes Pareto-Like Effect in Stimulated T Cell Populations.

Cosette, Jérémie / Moussy, Alice / Onodi, Fanny / Auffret-Cariou, Adrien / Neildez-Nguyen, Thi My Anh / Paldi, Andras / Stockholm, Daniel

Scientific reports

2015 Volume 5, Page(s) 17756

Abstract: Cell fate choice during the process of differentiation may obey to deterministic or stochastic rules. In order to discriminate between these two strategies we used time-lapse microscopy of individual murine CD4 + T cells that allows investigating the ... ...

Abstract	Cell fate choice during the process of differentiation may obey to deterministic or stochastic rules. In order to discriminate between these two strategies we used time-lapse microscopy of individual murine CD4 + T cells that allows investigating the dynamics of proliferation and fate commitment. We observed highly heterogeneous division and death rates between individual clones resulting in a Pareto-like dominance of a few clones at the end of the experiment. Commitment to the Treg fate was monitored using the expression of a GFP reporter gene under the control of the endogenous Foxp3 promoter. All possible combinations of proliferation and differentiation were observed and resulted in exclusively GFP-, GFP+ or mixed phenotype clones of very different population sizes. We simulated the process of proliferation and differentiation using a simple mathematical model of stochastic decision-making based on the experimentally observed parameters. The simulations show that a stochastic scenario is fully compatible with the observed Pareto-like imbalance in the final population.
MeSH term(s)	Algorithms ; Animals ; Cell Differentiation ; Cell Proliferation ; Cell Survival ; Cells, Cultured ; Computer Simulation ; Mice ; Microscopy, Fluorescence ; Models, Biological ; Phenotype ; T-Lymphocyte Subsets/metabolism
Language	English
Publishing date	2015-12-09
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/srep17756
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Article: High Therapeutic Efficacy of a New Survivin LSP-Cancer Vaccine Containing CD4

Onodi, Fanny / Maherzi-Mechalikh, Chahrazed / Mougel, Alice / Ben Hamouda, Nadine / Taboas, Charlotte / Gueugnon, Fabien / Tran, Thi / Nozach, Herve / Marcon, Elodie / Gey, Alain / Terme, Magali / Bouzidi, Ahmed / Maillere, Bernard / Kerzerho, Jérôme / Tartour, Eric / Tanchot, Corinne

Frontiers in oncology

2018 Volume 8, Page(s) 517

Abstract: The efficacy of an antitumoral vaccine relies both on the choice of the antigen targeted and on its design. The tumor antigen survivin is an attractive target to develop therapeutic cancer vaccines because of its restricted over-expression and vital ... ...

Abstract	The efficacy of an antitumoral vaccine relies both on the choice of the antigen targeted and on its design. The tumor antigen survivin is an attractive target to develop therapeutic cancer vaccines because of its restricted over-expression and vital functions in most human tumors. Accordingly, several clinical trials targeting survivin in various cancer indications have been conducted. Most of them relied on short peptide-based vaccines and showed promising, but limited clinical results. In this study, we investigated the immunogenicity and therapeutic efficacy of a new long synthetic peptide (LSP)-based cancer vaccine targeting the tumor antigen survivin (SVX). This SVX vaccine is composed of three long synthetic peptides containing several CD4
Language	English
Publishing date	2018-11-13
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2649216-7
ISSN	2234-943X
ISSN	2234-943X
DOI	10.3389/fonc.2018.00517
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Article ; Online: Inborn errors of type I IFN immunity in patients with life-threatening COVID-19

Zhang, Qian / Bastard, Paul / Liu, Zhiyong / Le Pen, Jérémie / Moncada-Velez, Marcela / Chen, Jie / Ogishi, Masato / Sabli, Ira K.D. / Hodeib, Stephanie / Korol, Cecilia / Rosain, Jérémie / Bilguvar, Kaya / Ye, Junqiang / Bolze, Alexandre / Bigio, Benedetta / Yang, Rui / Arias, Andrés Augusto / Zhou, Qinhua / Zhang, Yu /

Onodi, Fanny / Korniotis, Sarantis / Karpf, Léa / Philippot, Quentin / Chbihi, Marwa / Bonnet-Madin, Lucie / Dorgham, Karim / Smith, Nikaïa / Schneider, William M. / Razooky, Brandon S. / Hoffmann, Hans Heinrich / Michailidis, Eleftherios / Moens, Leen / Han, Ji Eun / Lorenzo, Lazaro / Bizien, Lucy / Meade, Philip / Neehus, Anna Lena / Ugurbil, Aileen Camille / Corneau, Aurélien / Kerner, Gaspard / Zhang, Peng / Rapaport, Franck / Seeleuthner, Yoann / Manry, Jeremy / Masson, Cecile / Schmitt, Yohann / Schlüter, Agatha / Li, Juan / Mogensen, Trine H. / Casanova, Jean Laurent

Zhang , Q , Bastard , P , Liu , Z , Le Pen , J , Moncada-Velez , M , Chen , J , Ogishi , M , Sabli , I K D , Hodeib , S , Korol , C , Rosain , J , Bilguvar , K , Ye , J , Bolze , A , Bigio , B , Yang , R , Arias , A A , Zhou , Q , Zhang , Y , Onodi , F , Korniotis , S , Karpf , L , Philippot , Q , Chbihi , M , Bonnet-Madin , L , Dorgham , K , Smith , N , Schneider , W M , Razooky , B S , Hoffmann , H H , Michailidis , E , Moens , L , Han , J E , Lorenzo , L , Bizien , L , Meade , P , Neehus , A L , Ugurbil , A C , Corneau , A , Kerner , G , Zhang , P , Rapaport , F , Seeleuthner , Y , Manry , J , Masson , C , Schmitt , Y , Schlüter , A , Li , J , Mogensen , T H , Casanova , J L , COVID-STORM Clinicians , COVID Clinicians , Imagine COVID Group , French COVID Cohort Study Group , CoV-Contact Cohort , Amsterdam UMC Covid-19 Biobank , COVID Human Genetic Effort & NIAID-USUHS/TAGC COVID Immunity Group 2020 , ' Inborn errors of type I IFN immunity in patients with life-threatening COVID-19 ' , Science , vol. 370 , no. 6515 . https://doi.org/10.1126/science.abd4570

2020

Abstract: Clinical outcome upon infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ranges from silent infection to lethal coronavirus disease 2019 (COVID-19). We have found an enrichment in rare variants predicted to be loss-of-function ( ... ...

Abstract	Clinical outcome upon infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ranges from silent infection to lethal coronavirus disease 2019 (COVID-19). We have found an enrichment in rare variants predicted to be loss-of-function (LOF) at the 13 human loci known to govern Toll-like receptor 3 (TLR3)- and interferon regulatory factor 7 (IRF7)-dependent type I interferon (IFN) immunity to influenza virus in 659 patients with life-threatening COVID-19 pneumonia relative to 534 subjects with asymptomatic or benign infection. By testing these and other rare variants at these 13 loci, we experimentally defined LOF variants underlying autosomal-recessive or autosomal-dominant deficiencies in 23 patients (3.5%) 17 to 77 years of age. We show that human fibroblasts with mutations affecting this circuit are vulnerable to SARS-CoV-2. Inborn errors of TLR3- and IRF7-dependent type I IFN immunity can underlie life-threatening COVID-19 pneumonia in patients with no prior severe infection.
Keywords	covid19
Subject code	616
Language	English
Publishing country	dk
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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