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  1. Article ; Online: Author Correction

    Leticia Laura Niborski / Paul Gueguen / Mengliang Ye / Allan Thiolat / Rodrigo Nalio Ramos / Pamela Caudana / Jordan Denizeau / Ludovic Colombeau / Raphaël Rodriguez / Christel Goudot / Jean-Michel Luccarini / Anne Soudé / Bruno Bournique / Pierre Broqua / Luigia Pace / Sylvain Baulande / Christine Sedlik / Jean-Pierre Quivy / Geneviève Almouzni /
    José L. Cohen / Elina Zueva / Joshua J. Waterfall / Sebastian Amigorena / Eliane Piaggio

    Nature Communications, Vol 14, Iss 1, Pp 1-

    CD8+T cell responsiveness to anti-PD-1 is epigenetically regulated by Suv39h1 in melanomas

    2023  Volume 1

    Keywords Science ; Q
    Language English
    Publishing date 2023-05-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: CD8+T cell responsiveness to anti-PD-1 is epigenetically regulated by Suv39h1 in melanomas

    Leticia Laura Niborski / Paul Gueguen / Mengliang Ye / Allan Thiolat / Rodrigo Nalio Ramos / Pamela Caudana / Jordan Denizeau / Ludovic Colombeau / Raphaël Rodriguez / Christel Goudot / Jean-Michel Luccarini / Anne Soudé / Bruno Bournique / Pierre Broqua / Luigia Pace / Sylvain Baulande / Christine Sedlik / Jean-Pierre Quivy / Geneviève Almouzni /
    José L. Cohen / Elina Zueva / Joshua J. Waterfall / Sebastian Amigorena / Eliane Piaggio

    Nature Communications, Vol 13, Iss 1, Pp 1-

    2022  Volume 16

    Abstract: Abstract Tumor-infiltrating CD8 + T cells progressively lose functionality and fail to reject tumors. The underlying mechanism and re-programing induced by checkpoint blockers are incompletely understood. We show here that genetic ablation or ... ...

    Abstract Abstract Tumor-infiltrating CD8 + T cells progressively lose functionality and fail to reject tumors. The underlying mechanism and re-programing induced by checkpoint blockers are incompletely understood. We show here that genetic ablation or pharmacological inhibition of histone lysine methyltransferase Suv39h1 delays tumor growth and potentiates tumor rejection by anti-PD-1. In the absence of Suv39h1, anti-PD-1 induces alternative activation pathways allowing survival and differentiation of IFNγ and Granzyme B producing effector cells that express negative checkpoint molecules, but do not reach final exhaustion. Their transcriptional program correlates with that of melanoma patients responding to immune-checkpoint blockade and identifies the emergence of cytolytic-effector tumor-infiltrating lymphocytes as a biomarker of clinical response. Anti-PD-1 favors chromatin opening in loci linked to T-cell activation, memory and pluripotency, but in the absence of Suv39h1, cells acquire accessibility in cytolytic effector loci. Overall, Suv39h1 inhibition enhances anti-tumor immune responses, alone or combined with anti-PD-1, suggesting that Suv39h1 is an “epigenetic checkpoint” for tumor immunity.
    Keywords Science ; Q
    Subject code 570
    Language English
    Publishing date 2022-06-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Induction of anergic or regulatory tumor-specific CD4+ T cells in the tumor-draining lymph node

    Ruby Alonso / Héloïse Flament / Sébastien Lemoine / Christine Sedlik / Emanuel Bottasso / Isabel Péguillet / Virginie Prémel / Jordan Denizeau / Marion Salou / Aurélie Darbois / Nicolás Gonzalo Núñez / Benoit Salomon / David Gross / Eliane Piaggio / Olivier Lantz

    Nature Communications, Vol 9, Iss 1, Pp 1-

    2018  Volume 17

    Abstract: Tumor neoantigens can be drained to the lymph nodes, but the nature and the significance of the induced immune responses are still unclear. Here the authors use a mouse genetic tumor model to show that tumor-specific CD4 T cells can become anergic or ... ...

    Abstract Tumor neoantigens can be drained to the lymph nodes, but the nature and the significance of the induced immune responses are still unclear. Here the authors use a mouse genetic tumor model to show that tumor-specific CD4 T cells can become anergic or suppressive in the draining lymph node to modulate tumor immunity.
    Keywords Science ; Q
    Language English
    Publishing date 2018-05-01T00:00:00Z
    Publisher Nature Publishing Group
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: Induction of anergic or regulatory tumor-specific CD4+ T cells in the tumor-draining lymph node

    Ruby Alonso / Héloïse Flament / Sébastien Lemoine / Christine Sedlik / Emanuel Bottasso / Isabel Péguillet / Virginie Prémel / Jordan Denizeau / Marion Salou / Aurélie Darbois / Nicolás Gonzalo Núñez / Benoit Salomon / David Gross / Eliane Piaggio / Olivier Lantz

    Nature Communications, Vol 9, Iss 1, Pp 1-

    2018  Volume 17

    Abstract: Tumor neoantigens can be drained to the lymph nodes, but the nature and the significance of the induced immune responses are still unclear. Here the authors use a mouse genetic tumor model to show that tumor-specific CD4 T cells can become anergic or ... ...

    Abstract Tumor neoantigens can be drained to the lymph nodes, but the nature and the significance of the induced immune responses are still unclear. Here the authors use a mouse genetic tumor model to show that tumor-specific CD4 T cells can become anergic or suppressive in the draining lymph node to modulate tumor immunity.
    Keywords Science ; Q
    Language English
    Publishing date 2018-05-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article: Heparan sulfates targeting increases MHC class I- and MHC class II-restricted antigen presentation and CD8+ T-cell response

    Knittel, Delphine / Adeline Gadzinski / Alexandra Savatier / Christine Sedlik / Eliane Piaggio / Jean-Claude Boulain / Jordan Denizeau / Michel Léonetti / Philippe de la Rochère / Sebastian Amigorena / Stéphane Hua

    Vaccine. 2016 June 08, v. 34, no. 27

    2016  

    Abstract: Heparan sulfates (HS) are carbohydrate moieties of HS proteoglycans (HSPGs). They often represent alternative attachment points for proteins or microorganisms targeting receptors. HSPGs, which are ubiquitously expressed, thereby participate in numerous ... ...

    Abstract Heparan sulfates (HS) are carbohydrate moieties of HS proteoglycans (HSPGs). They often represent alternative attachment points for proteins or microorganisms targeting receptors. HSPGs, which are ubiquitously expressed, thereby participate in numerous biological processes. We previously showed that MHC class II-restricted antigen presentation is increased when antigens are coupled to HS ligands, suggesting that HSPGs might contribute to adaptive immune responses. Here, we examined if HSPG targeting influences other aspects of immune responses. We found that coupling of an HS ligand to the antigen increases antigen presentation to CD4+ and CD8+ T-cells after antigen targeting to membrane immunoglobulins or to MHC-II molecules. Moreover, this increased stimulating capacity correlates with an enhanced CD8+ immune response in mice. Last, animals control more effectively the growth of Ova-expressing tumour cells when they are immunized with an Ova construct targeting HSPGs and MHC-II molecules. Our results indicate that ubiquitous molecules can influence both MHC class I- and MHC class II-restricted antigen presentation and behave as co-receptors during T-cell stimulation. Moreover, they suggest that tumour-antigens endowed with the ability to target both HSPGs and MHC-II molecules could be of value to increase CD8+ immune response and control tumour-growth, opening new perspectives for the design of highly immunogenic protein-based vaccines.
    Keywords antigen presentation ; antigens ; CD8-positive T-lymphocytes ; immune response ; immunoglobulins ; ligands ; mice ; microorganisms ; neoplasm cells ; proteoglycans ; receptors ; sulfates ; vaccines
    Language English
    Dates of publication 2016-0608
    Size p. 3093-3101.
    Publishing place Elsevier Ltd
    Document type Article
    ZDB-ID 605674-x
    ISSN 1873-2518 ; 0264-410X
    ISSN (online) 1873-2518
    ISSN 0264-410X
    DOI 10.1016/j.vaccine.2016.04.073
    Database NAL-Catalogue (AGRICOLA)

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  6. Article ; Online: Different immunogenicity but similar antitumor efficacy of two DNA vaccines coding for an antigen secreted in different membrane vesicle-associated forms

    Christine Sedlik / James Vigneron / Lea Torrieri-Dramard / Fabien Pitoiset / Jordan Denizeau / Caroline Chesneau / Philippe de la Rochere / Olivier Lantz / Clotilde Thery / Bertrand Bellier

    Journal of Extracellular Vesicles, Vol 3, Iss 0, Pp 1-

    2014  Volume 13

    Abstract: The induction of an active immune response to control or eliminate tumours is still an unfulfilled challenge. We focused on plasmid DNA vaccines using an innovative approach whereby the antigen is expressed in association with extracellular vesicles (EVs) ...

    Abstract The induction of an active immune response to control or eliminate tumours is still an unfulfilled challenge. We focused on plasmid DNA vaccines using an innovative approach whereby the antigen is expressed in association with extracellular vesicles (EVs) to facilitate antigen cross-presentation and improve induced immunity. Our two groups had independently shown previously that DNA vaccines encoding EV-associated antigens are more efficient at inducing cytotoxic T-cell responses than vaccines encoding the non-EV-associated antigen. Here, we compared our two approaches to associate the ovalbumin (OVA) antigen to EVs: (a) by fusion to the lipid-binding domain C1C2 of MFGE8(=lactadherin), which is exposed on the surface of secreted membrane vesicles; and (b) by fusion to retroviral Gag capsid protein, which is incorporated inside membrane-enclosed virus-like particles. Plasmids encoding either form of modified OVA were used as DNA-based vaccines (i.e. injected into mice to allow in vivo expression of the antigen associated to EVs). We show that both DNA vaccines induced, with similar efficiency, OVA-specific CD8+ T cells and total IgG antibodies. By contrast, each vaccine preferentially stimulated different isotypes of immunoglobulins, and the OVA-C1C2-encoding vaccine favoured antigen-specific CD4+ T lymphocyte induction as compared to the Gag-OVA vaccine. Nevertheless, both OVA-C1C2 and Gag-OVA vaccines efficiently prevented in vivo outgrowth of OVA-expressing tumours and reduced tumour progression when administered to tumour-bearing mice, although with variable efficacies depending on the tumour models. DNA vaccines encoding EV-associated antigens are thus promising immunotherapy tools in cancer but also potentially other diseases.
    Keywords extracellular vesicles ; microvesicles ; exosomes ; virus-like particles ; tumour immunity ; vaccination ; Biology (General) ; QH301-705.5 ; Science ; Q
    Subject code 570
    Language English
    Publishing date 2014-08-01T00:00:00Z
    Publisher Co-Action Publishing
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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