المؤلفون: Mastelic-Gavillet, Beatris, Sarivalasis, Apostolos, Lozano, Leyder Elena, Lofek, Sebastien, Wyss, Tania, Melero, Ignacio, de Vries, I. Jolanda M., Harari, Alexandre, Romero, Pedro, Kandalaft, Lana Elias, Viganó, Selena

المصدر: Frontiers in Immunology ; volume 14 ; ISSN 1664-3224

مصطلحات موضوعية: Immunology, Immunology and Allergy

الوصف: Background The use of circulating cDC1 to generate anti-cancer vaccines is among the most promising approaches to overcome the limited immunogenicity and clinical efficacy of monocyte-derived DC. However, the recurrent lymphopenia and the reduction of DC numbers and functionality in patients with cancer may represent an important limitation of such approach. In patients with ovarian cancer (OvC) that had received chemotherapy, we previously showed that cDC1 frequency and function were reduced. Methods We recruited healthy donors (HD, n=7) and patients with OvC at diagnosis and undergoing interval debulking surgery (IDS, n=6), primary debulking surgery (PDS, n=6) or at relapse (n=8). We characterized longitudinally phenotypic and functional properties of peripheral DC subsets by multiparametric flow cytometry. Results We show that the frequency of cDC1 and the total CD141+ DC capacity to take up antigen are not reduced at the diagnosis, while their TLR3 responsiveness is partially impaired in comparison with HD. Chemotherapy causes cDC1 depletion and increase in cDC2 frequency, but mainly in patients belonging to the PDS group, while in the IDS group both total lymphocytes and cDC1 are preserved. The capacity of total CD141 + DC and cDC2 to take up antigen is not impacted by chemotherapy, while the activation capacity upon Poly(I:C) (TLR3L) stimulation is further decreased. Conclusions Our study provides new information about the impact of chemotherapy on the immune system of patients with OvC and sheds a new light on the importance of considering timing with respect to chemotherapy when designing new vaccination strategies that aim at withdrawing or targeting specific DC subsets.

الإتاحة: https://doi.org/10.3389/fimmu.2023.1119371Test

المؤلفون: Hua, Stéphane, Vigano, Selena, Tse, Samantha, Zhengyu, Ouyang, Harrington, Sean, Negron, Jordi, Garcia-Broncano, Pilar, Marchetti, Giulia, Genebat, Miguel, Leal, Manuel, Resino, Salvador, Ruiz-Mateos, Ezequiel, Lichterfeld, Mathias, Yu, Xu G.

المصدر: Clinical Infectious Diseases, 2018 Jun . 66(12), 1910-1917.

الوصول الحر: https://www.jstor.org/stable/26526325Test

المؤلفون: Offersen, Rasmus, Yu, Wen-Han, Scully, Eileen P, Julg, Boris, Euler, Zelda, Sadanand, Saheli, Garcia-Dominguez, Dario, Zheng, Lu, Rasmussen, Thomas A, Jennewein, Madeleine F, Linde, Caitlyn, Sassic, Jessica, Lofano, Giuseppe, Vigano, Selena, Stephenson, Kathryn E, Fischinger, Stephanie, Suscovich, Todd J, Lichterfeld, Mathias, Lauffenburger, Douglas, Rosenberg, Erik S, Allen, Todd, Altfeld, Marcus, Charles, Richelle C, Østergaard, Lars, Tolstrup, Martin, Barouch, Dan H, Søgaard, Ole S, Alter, Galit

المساهمون: Ragon Institute of MGH, MIT and Harvard, Massachusetts Institute of Technology. Department of Biological Engineering

المصدر: Elsevier

الوصف: © 2020 The Authors Changes in antibody glycosylation are linked to inflammation across several diseases. Alterations in bulk antibody galactosylation can predict rheumatic flares, act as a sensor for immune activation, predict gastric cancer relapse, track with biological age, shift with vaccination, change with HIV reservoir size on therapy, and decrease in HIV and HCV infections. However, whether changes in antibody Fc biology also track with reservoir rebound time remains unclear. The identification of a biomarker that could forecast viral rebound time could significantly accelerate the downselection and iterative improvement of promising HIV viral eradication strategies. Using a comprehensive antibody Fc-profiling approach, the level of HIV-specific antibody Fc N-galactosylation is significantly associated with time to rebound after treatment discontinuation across three independent cohorts. Thus virus-specific antibody glycosylation may represent a promising, simply measured marker to track reservoir reactivation.

وصف الملف: application/pdf

العلاقة: Cell Reports; https://hdl.handle.net/1721.1/136136Test

الإتاحة: https://hdl.handle.net/1721.1/136136Test

المؤلفون: Cappuccini, Federica, Bryant, Richard, Pollock, Emily, Carter, Lucy, Verrill, Clare, Hollidge, Julianne, Poulton, Ian, Baker, Megan, Mitton, Celia, Baines, Andrea, Meier, Armin, Schmidt, Guenter, Harrop, Richard, Protheroe, Andrew, MacPherson, Ruth, Kennish, Steven, Morgan, Susan, Vigano, Selena, Romero, Pedro J, Evans, Thomas, Catto, James, Hamdy, Freddie, Hill, Adrian V S, Redchenko, Irina

المساهمون: European Commission

المصدر: Journal for ImmunoTherapy of Cancer ; volume 8, issue 1, page e000928 ; ISSN 2051-1426

الوصف: Background Prostate cancer (PCa) has been under investigation as a target for antigen-specific immunotherapies in metastatic disease settings for the last two decades leading to a licensure of the first therapeutic cancer vaccine, Sipuleucel-T, in 2010. However, neither Sipuleucel-T nor other experimental PCa vaccines that emerged later induce strong T-cell immunity. Methods In this first-in-man study, VANCE, we evaluated a novel vaccination platform based on two replication-deficient viruses, chimpanzee adenovirus (ChAd) and MVA (Modified Vaccinia Ankara), targeting the oncofetal self-antigen 5T4 in early stage PCa. Forty patients, either newly diagnosed with early-stage PCa and scheduled for radical prostatectomy or patients with stable disease on an active surveillance protocol, were recruited to the study to assess the vaccine safety and T-cell immunogenicity. Secondary and exploratory endpoints included immune infiltration into the prostate, prostate-specific antigen (PSA) change, and assessment of phenotype and functionality of antigen-specific T cells. Results The vaccine had an excellent safety profile. Vaccination-induced 5T4-specific T-cell responses were measured in blood by ex vivo IFN-γ ELISpot and were detected in the majority of patients with a mean level in responders of 198 spot-forming cells per million peripheral blood mononuclear cells. Flow cytometry analysis demonstrated the presence of both CD8+ and CD4+ polyfunctional 5T4-specific T cells in the circulation. 5T4-reactive tumor-infiltrating lymphocytes were isolated from post-treatment prostate tissue. Some of the patients had a transient PSA rise 2–8 weeks following vaccination, possibly indicating an inflammatory response in the target organ. Conclusions An excellent safety profile and T-cell responses elicited in the circulation and also detected in the prostate gland support the evaluation of the ChAdOx1-MVA 5T4 vaccine in efficacy trials. It remains to be seen if this vaccination strategy generates immune responses of sufficient ...

الإتاحة: https://doi.org/10.1136/jitc-2020-000928Test

المؤلفون: Vigano, Selena, Bobisse, Sara, Coukos, George, Perreau, Matthieu, Harari, Alexandre

المصدر: Frontiers in Immunology ; volume 11 ; ISSN 1664-3224

مصطلحات موضوعية: Immunology, Immunology and Allergy

الإتاحة: https://doi.org/10.3389/fimmu.2020.01350Test

المؤلفون: Offersen, Rasmus, Yu, Wen-Han, Scully, Eileen P., Julg, Boris, Euler, Zelda, Sadanand, Saheli, Garcia-Dominguez, Dario, Zheng, Lu, Rasmussen, Thomas A., Jennewein, Madeleine F., Linde, Caitlyn, Sassic, Jessica, Lofano, Giuseppe, Vigano, Selena, Stephenson, Kathryn E., Fischinger, Stephanie, Suscovich, Todd J., Lichterfeld, Mathias, Lauffenburger, Douglas, Rosenberg, Erik S., Allen, Todd, Altfeld, Marcus, Charles, Richelle C., Østergaard, Lars, Tolstrup, Martin, Barouch, Dan H., Søgaard, Ole S., Alter, Galit

المساهمون: Massachusetts General Hospital

المصدر: Cell Reports ; volume 33, issue 11, page 108502 ; ISSN 2211-1247

مصطلحات موضوعية: General Biochemistry, Genetics and Molecular Biology

الإتاحة: https://doi.org/10.1016/j.celrep.2020.108502Test
https://api.elsevier.com/content/article/PII:S2211124720314911?httpAccept=text/xmlTest
https://api.elsevier.com/content/article/PII:S2211124720314911?httpAccept=text/plainTest

المؤلفون: Mastelic-Gavillet, Beatris, Sarivalasis, Apostolos, Lozano, Leyder Elena, Wyss, Tania, Inoges, Susana, de Vries, Ingrid Jolanda Monique, Dartiguenave, Florence, Jichlinski, Patrice, Derrè, Laurent, Coukos, George, Melero, Ignacio, Harari, Alexandre, Romero, Pedro, Viganó, Selena, Kandalaft, Lana Elias

المساهمون: Horizon 2020

المصدر: European Journal of Cancer ; volume 135, page 173-182 ; ISSN 0959-8049

مصطلحات موضوعية: Cancer Research, Oncology

الإتاحة: https://doi.org/10.1016/j.ejca.2020.04.036Test
https://api.elsevier.com/content/article/PII:S0959804920302409?httpAccept=text/xmlTest
https://api.elsevier.com/content/article/PII:S0959804920302409?httpAccept=text/plainTest

المؤلفون: Mastelic-Gavillet, Beatris, Navarro Rodrigo, Blanca, Décombaz, Laure, Wang, Haiping, Ercolano, Giuseppe, Ahmed, Rita, Lozano, Leyder Elena, Ianaro, Angela, Derré, Laurent, Valerio, Massimo, Tawadros, Thomas, Jichlinski, Patrice, Nguyen-Ngoc, Tu, Speiser, Daniel E., Verdeil, Grégory, Gestermann, Nicolas, Dormond, Olivier, Kandalaft, Lana, Coukos, George, Jandus, Camilla, Ménétrier-Caux, Christine, Caux, Christophe, Ho, Ping-Chih, Romero, Pedro, Harari, Alexandre, Vigano, Selena

المصدر: Journal for ImmunoTherapy of Cancer 7(1) 257

مصطلحات موضوعية: Adenosine, CD8 T cells, Metabolism, mTOR, TILs

الوصف: Background: Several mechanisms are present in the tumor microenvironment (TME) to impair cytotoxic T cell responses potentially able to control tumor growth. Among these, the accumulation of adenosine (Ado) contributes to tumor progression and represents a promising immunotherapeutic target. Ado has been shown to impair T cell effector function, but the role and mechanisms employed by Ado/Ado receptors (AdoRs) in modulating human peripheral and tumor-infiltrating lymphocyte (TIL) function are still puzzling.Methods: CD8+ T cell cytokine production following stimulation was quantified by intracellular staining and flow cytometry. The cytotoxic capacity of tumor infiltrating lymphocytes (TILs) was quantified by the chromium release assay following co-culture with autologous or anti-CD3-loaded tumor cell lines. The CD8+ T cell metabolic fitness was evaluated by the seahorse assay and by the quantification of 2-NBDG uptake and CD71/CD98 upregulation upon stimulation. The expression of AdoRs was assessed by RNA flow cytometry, a recently developed technology that we validated by semiquantitative RT-PCR (qRT-PCR), while the impact on T cell function was evaluated by the use of selective antagonists and agonists. The influence of Ado/AdoR on the PKA and mTOR pathways was evaluated by phosphoflow staining of p-CREB and p-S6, respectively, and validated by western blot.Results: Here, we demonstrate that Ado signaling through the A2A receptor (A2AR) in human peripheral CD8+ T cells and TILs is responsible for the higher sensitivity to Ado-mediated suppression of T central memory cells. We confirmed that Ado is able to impair peripheral and tumor-expanded T cell effector functions, and we show for the first time its impact on metabolic fitness. The Ado-mediated immunosuppressive effects are mediated by increased PKA activation that results in impairment of the mTORC1 pathway.Conclusions: Our findings unveil A2AR/PKA/mTORC1 as the main Ado signaling pathway impairing the immune competence of peripheral T cells and TILs. ...

العلاقة: info:eu-repo/grantAgreement/EC/FP7/602200/; https://zenodo.org/communities/fp7-bmcTest; https://zenodo.org/record/3484176Test; https://doi.org/10.1186/s40425-019-0719-5Test; oai:zenodo.org:3484176

الإتاحة: https://doi.org/10.1186/s40425-019-0719-5Test
https://zenodo.org/record/3484176Test

المؤلفون: Vigano, Selena, Alatzoglou, Dimitrios, Irving, Melita, Ménétrier-Caux, Christine, Caux, Christophe, Romero, Pedro, Coukos, George

المساهمون: Centre Hospitalier Universitaire Vaudois = Lausanne University Hospital Lausanne (CHUV), Université de Lausanne = University of Lausanne (UNIL), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard Lyon -Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)

المصدر: ISSN: 1664-3224.

مصطلحات موضوعية: [SDV]Life Sciences [q-bio]

الوصف: International audience

العلاقة: hal-03769096; https://hal.science/hal-03769096Test; https://hal.science/hal-03769096/documentTest; https://hal.science/hal-03769096/file/fimmu-10-00925.pdfTest

الإتاحة: https://doi.org/10.3389/fimmu.2019.00925Test
https://hal.science/hal-03769096Test
https://hal.science/hal-03769096/documentTest
https://hal.science/hal-03769096/file/fimmu-10-00925.pdfTest

المؤلفون: Rozot, Virginie, Patrizia, Amelio, Vigano, Selena, Mazza-Stalder, Jesica, Idrizi, Elita, Day, Cheryl L., Perreau, Matthieu, Lazor-Blanchet, Catherine, Ohmiti, Khalid, Goletti, Delia, Bart, Pierre-Alexandre, Hanekom, Willem, Scriba, Thomas J., Nicod, Laurent, Pantaleo, Giuseppe, Harari, Alexandre

المصدر: Clinical Infectious Diseases, 2015 Feb 01. 60(3), 432-437.

الوصول الحر: https://www.jstor.org/stable/26362921Test