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  1. Article ; Online: Immune Signature Linked to COVID-19 Severity

    Jules Russick / Pierre-Emmanuel Foy / Nathalie Josseaume / Maxime Meylan / Nadine Ben Hamouda / Amos Kirilovsky / Carine El Sissy / Eric Tartour / David M. Smadja / Alexandre Karras / Jean-Sébastien Hulot / Marine Livrozet / Antoine Fayol / Jean-Benoit Arlet / Jean-Luc Diehl / Marie-Agnès Dragon-Durey / Franck Pagès / Isabelle Cremer

    Frontiers in Immunology, Vol

    A SARS-Score for Personalized Medicine

    2021  Volume 12

    Abstract: SARS-CoV-2 infection leads to a highly variable clinical evolution, ranging from asymptomatic to severe disease with acute respiratory distress syndrome, requiring intensive care units (ICU) admission. The optimal management of hospitalized patients has ... ...

    Abstract SARS-CoV-2 infection leads to a highly variable clinical evolution, ranging from asymptomatic to severe disease with acute respiratory distress syndrome, requiring intensive care units (ICU) admission. The optimal management of hospitalized patients has become a worldwide concern and identification of immune biomarkers predictive of the clinical outcome for hospitalized patients remains a major challenge. Immunophenotyping and transcriptomic analysis of hospitalized COVID-19 patients at admission allow identifying the two categories of patients. Inflammation, high neutrophil activation, dysfunctional monocytic response and a strongly impaired adaptive immune response was observed in patients who will experience the more severe form of the disease. This observation was validated in an independent cohort of patients. Using in silico analysis on drug signature database, we identify differential therapeutics that specifically correspond to each group of patients. From this signature, we propose a score—the SARS-Score—composed of easily quantifiable biomarkers, to classify hospitalized patients upon arrival to adapt treatment according to their immune profile.
    Keywords COVID-19 ; immunologic profile ; personalized medicine/personalized health care ; score ; therapeutic strategy ; Immunologic diseases. Allergy ; RC581-607
    Subject code 616 ; 610
    Language English
    Publishing date 2021-07-01T00:00:00Z
    Publisher Frontiers Media S.A.
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Differential association between inflammatory cytokines and multiorgan dysfunction in COVID-19 patients with obesity.

    Marie-Agnès Dragon-Durey / Xiaoyi Chen / Amos Kirilovsky / Nadine Ben Hamouda / Carine El Sissy / Jules Russick / Etienne Charpentier / Yannick Binois / Florence Marliot / Maxime Meylan / Clémence Granier / Hélène Pere / Antonin Saldmann / Bastien Rance / Anne Sophie Jannot / Stéphanie Baron / Mouna Chebbi / Antoine Fayol / Nathalie Josseaume /
    Claire Rives-Lange / Pierre-Louis Tharaux / Bernard Cholley / Jean-Luc Diehl / Jean-Benoît Arlet / Michel Azizi / Alexandre Karras / Sébastien Czernichow / David M Smadja / Jean-Sébastien Hulot / Isabelle Cremer / Eric Tartour / Elie Mousseaux / Franck Pagès

    PLoS ONE, Vol 16, Iss 5, p e

    2021  Volume 0252026

    Abstract: To investigate the mechanisms underlying the SARS-CoV-2 infection severity observed in patients with obesity, we performed a prospective study of 51 patients evaluating the impact of multiple immune parameters during 2 weeks after admission, on vital ... ...

    Abstract To investigate the mechanisms underlying the SARS-CoV-2 infection severity observed in patients with obesity, we performed a prospective study of 51 patients evaluating the impact of multiple immune parameters during 2 weeks after admission, on vital organs' functions according to body mass index (BMI) categories. High-dimensional flow cytometric characterization of immune cell subsets was performed at admission, 30 systemic cytokines/chemokines levels were sequentially measured, thirteen endothelial markers were determined at admission and at the zenith of the cytokines. Computed tomography scans on admission were quantified for lung damage and hepatic steatosis (n = 23). Abnormal BMI (> 25) observed in 72.6% of patients, was associated with a higher rate of intensive care unit hospitalization (p = 0.044). SARS-CoV-2 RNAaemia, peripheral immune cell subsets and cytokines/chemokines were similar among BMI groups. A significant association between inflammatory cytokines and liver, renal, and endothelial dysfunctions was observed only in patients with obesity (BMI > 30). In contrast, early signs of lung damage (ground-glass opacity) correlated with Th1/M1/inflammatory cytokines only in normal weight patients. Later lesions of pulmonary consolidation correlated with BMI but were independent of cytokine levels. Our study reveals distinct physiopathological mechanisms associated with SARS-CoV-2 infection in patients with obesity that may have important clinical implications.
    Keywords Medicine ; R ; Science ; Q
    Subject code 610 ; 616
    Language English
    Publishing date 2021-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Characterization of the Microenvironment in Positive and Negative Sentinel Lymph Nodes from Melanoma Patients.

    Meriem Messaoudene / Aurélie Périer / Giulia Fregni / Emmanuelle Neves / Laurence Zitvogel / Isabelle Cremer / Johan Chanal / Xavier Sastre-Garau / Lydia Deschamps / Eduardo Marinho / Frederique Larousserie / Eve Maubec / Marie-Françoise Avril / Anne Caignard

    PLoS ONE, Vol 10, Iss 7, p e

    2015  Volume 0133363

    Abstract: Melanomas are aggressive skin tumors characterized by high metastatic potential. Our previous results indicate that Natural Killer (NK) cells may control growth of melanoma. The main defect of blood NK cells was a decreased expression of activating NCR1/ ... ...

    Abstract Melanomas are aggressive skin tumors characterized by high metastatic potential. Our previous results indicate that Natural Killer (NK) cells may control growth of melanoma. The main defect of blood NK cells was a decreased expression of activating NCR1/NKp46 receptor and a positive correlation of NKp46 expression with disease outcome in stage IV melanoma patients was found. In addition, in stage III melanoma patients, we identified a new subset of mature NK cells in macro-metastatic Lymph nodes (LN). In the present studies, we evaluated the numbers of NK cells infiltrating primary cutaneous melanoma and analyzed immune cell subsets in a series of sentinel lymph nodes (SLN). First, we show that NKp46+ NK cells infiltrate primary cutaneous melanoma. Their numbers were related to age of patients and not to Breslow thickness. Then, a series of patients with tumor-negative or -positive sentinel lymph nodes matched for Breslow thickness of the cutaneous melanoma was constituted. We investigated the distribution of macrophages (CD68), endothelial cells, NK cells, granzyme B positive (GrzB+) cells and CD8+ T cells in the SLN. Negative SLN (SLN-) were characterized by frequent adipose involution and follicular hyperplasia compared to positive SLN (SLN+). High densities of macrophages and endothelial cells (CD34), prominent in SLN+, infiltrate SLN and may reflect a tumor favorable microenvironment. Few but similar numbers of NK and GrzB+ cells were found in SLN- and SLN+: NK cells and GrzB+ cells were not correlated. Numerous CD8+ T cells infiltrated SLN with a trend for higher numbers in SLN-. Moreover, CD8+ T cells and GrzB+ cells correlated in SLN- not in SLN+. We also observed that the numbers of CD8+ T cells negatively correlated with endothelial cells in SLN-. The numbers of NK, GrzB+ or CD8+ T cells had no significant impact on overall survival. However, we found that the 5 year-relapse rate was higher in SLN with higher numbers of NK cells.
    Keywords Medicine ; R ; Science ; Q
    Subject code 610
    Language English
    Publishing date 2015-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: Immunodynamics of explanted human tumors for immuno‐oncology

    Agathe Dubuisson / Jean‐Eudes Fahrner / Anne‐Gaëlle Goubet / Safae Terrisse / Nicolas Voisin / Charles Bayard / Sebastien Lofek / Damien Drubay / Delphine Bredel / Séverine Mouraud / Sandrine Susini / Alexandria Cogdill / Lucas Rebuffet / Elise Ballot / Nicolas Jacquelot / Vincent Thomas de Montpreville / Odile Casiraghi / Camélia Radulescu / Sophie Ferlicot /
    David J Figueroa / Sapna Yadavilli / Jeremy D Waight / Marc Ballas / Axel Hoos / Thomas Condamine / Bastien Parier / Christophe Gaudillat / Bertrand Routy / François Ghiringhelli / Lisa Derosa / Ingrid Breuskin / Mathieu Rouanne / Fabrice André / Cédric Lebacle / Hervé Baumert / Marie Wislez / Elie Fadel / Isabelle Cremer / Laurence Albiges / Birgit Geoerger / Jean‐Yves Scoazec / Yohann Loriot / Guido Kroemer / Aurélien Marabelle / Mélodie Bonvalet / Laurence Zitvogel

    EMBO Molecular Medicine, Vol 13, Iss 1, Pp n/a-n/a (2021)

    2021  

    Abstract: Abstract Decision making in immuno‐oncology is pivotal to adapt therapy to the tumor microenvironment (TME) of the patient among the numerous options of monoclonal antibodies or small molecules. Predicting the best combinatorial regimen remains an unmet ... ...

    Abstract Abstract Decision making in immuno‐oncology is pivotal to adapt therapy to the tumor microenvironment (TME) of the patient among the numerous options of monoclonal antibodies or small molecules. Predicting the best combinatorial regimen remains an unmet medical need. Here, we report a multiplex functional and dynamic immuno‐assay based on the capacity of the TME to respond to ex vivo stimulation with twelve immunomodulators including immune checkpoint inhibitors (ICI) in 43 human primary tumors. This "in sitro" (in situ/in vitro) assay has the potential to predict unresponsiveness to anti‐PD‐1 mAbs, and to detect the most appropriate and personalized combinatorial regimen. Prospective clinical trials are awaited to validate this in sitro assay.
    Keywords “in sitro” assay ; cancer ; immune checkpoint inhibitors ; immunomonitoring ; precision oncology ; Medicine (General) ; R5-920 ; Genetics ; QH426-470
    Language English
    Publishing date 2021-01-01T00:00:00Z
    Publisher Wiley
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: Phenotypic and functional characteristics of blood natural killer cells from melanoma patients at different clinical stages.

    Giulia Fregni / Meriem Messaoudene / Emmanuelle Fourmentraux-Neves / Sarra Mazouz-Dorval / Johan Chanal / Eve Maubec / Eduardo Marinho / Isabelle Scheer-Senyarich / Isabelle Cremer / Marie-Françoise Avril / Anne Caignard

    PLoS ONE, Vol 8, Iss 10, p e

    2013  Volume 76928

    Abstract: Melanomas are aggressive skin tumors characterized by high metastatic potential. Immunotherapy is a valuable alternative for metastatic melanoma patients resistant to chemotherapy. Natural Killer (NK) cells are efficient anti-tumor cytotoxic effectors. ... ...

    Abstract Melanomas are aggressive skin tumors characterized by high metastatic potential. Immunotherapy is a valuable alternative for metastatic melanoma patients resistant to chemotherapy. Natural Killer (NK) cells are efficient anti-tumor cytotoxic effectors. We previously showed that blood NK cells from stage IV metastatic melanoma patients display decreased NK receptors and that chemotherapy modifies the functional status of blood NK cells. To investigate the role of NK cells along melanoma progression, we have here studied NK cells from patients at different stages of the disease. First, we showed that ex vivo NK cells from certain stage III-IV patients displayed low degranulation potential. Using a dynamic label-free assay, we found that immunoselected IL-2 activated blood NK cells from patients efficiently lysed melanoma cells through NKp46 and NKG2D receptors, independently to the clinical stage. Moreover, the ex vivo phenotype of circulating NK cells from 33 patients (stage I to IV) was extensively analyzed. NK cells from patients displayed higher variability in the percentages of Natural Cytotoxicity Receptors (NCR) and Natural Killer Group 2D (NKG2D) receptor expression compared to donor NK cells. The main defect was the decreased expression of NCR1 (NKp46) by NK cells from metastatic patients. Interestingly, we found a positive correlation between the NK cell percentages of NKp46 and the duration of stage IV in melanoma patients. Finally, we showed that NK cells infiltrated primary melanomas and displayed a predominant peritumoral distribution. These results are new arguments for the development of NK-based therapies in melanoma patients.
    Keywords Medicine ; R ; Science ; Q
    Subject code 610
    Language English
    Publishing date 2013-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article ; Online: Systemic inflammation, nutritional status and tumor immune microenvironment determine outcome of resected non-small cell lung cancer.

    Marco Alifano / Audrey Mansuet-Lupo / Filippo Lococo / Nicolas Roche / Antonio Bobbio / Emelyne Canny / Olivier Schussler / Hervé Dermine / Jean-François Régnard / Barbara Burroni / Jérémy Goc / Jérôme Biton / Hanane Ouakrim / Isabelle Cremer / Marie-Caroline Dieu-Nosjean / Diane Damotte

    PLoS ONE, Vol 9, Iss 9, p e

    2014  Volume 106914

    Abstract: BACKGROUND: Hypothesizing that nutritional status, systemic inflammation and tumoral immune microenvironment play a role as determinants of lung cancer evolution, the purpose of this study was to assess their respective impact on long-term survival in ... ...

    Abstract BACKGROUND: Hypothesizing that nutritional status, systemic inflammation and tumoral immune microenvironment play a role as determinants of lung cancer evolution, the purpose of this study was to assess their respective impact on long-term survival in resected non-small cell lung cancers (NSCLC). METHODS AND FINDINGS: Clinical, pathological and laboratory data of 303 patients surgically treated for NSCLC were retrospectively analyzed. C-reactive protein (CRP) and prealbumin levels were recorded, and tumoral infiltration by CD8+ lymphocytes and mature dendritic cells was assessed. We observed that factors related to nutritional status, systemic inflammation and tumoral immune microenvironment were correlated; significant correlations were also found between these factors and other relevant clinical-pathological parameters. With respect to outcome, at univariate analysis we found statistically significant associations between survival and the following variables: Karnofsky index, American Society of Anesthesiologists (ASA) class, CRP levels, prealbumin concentrations, extent of resection, pathologic stage, pT and pN parameters, presence of vascular emboli, and tumoral infiltration by either CD8+ lymphocytes or mature dendritic cells and, among adenocarcinoma type, tumor grade (all p<0.05). In multivariate analysis, prealbumin levels (Relative Risk (RR): 0.34 [0.16-0.73], p = 0.0056), CD8+ cell count in tumor tissue (RR = 0.37 [0.16-0.83], p = 0.0162), and disease stage (RR 1.73 [1.03-2.89]; 2.99[1.07-8.37], p = 0.0374- stage I vs II vs III-IV) were independent prognostic markers. When taken together, parameters related to systemic inflammation, nutrition and tumoral immune microenvironment allowed robust prognostic discrimination; indeed patients with undetectable CRP, high (>285 mg/L) prealbumin levels and high (>96/mm2) CD8+ cell count had a 5-year survival rate of 80% [60.9-91.1] as compared to 18% [7.9-35.6] in patients with an opposite pattern of values. When stages I-II were considered alone, the ...
    Keywords Medicine ; R ; Science ; Q
    Subject code 610 ; 616
    Language English
    Publishing date 2014-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  7. Article: Adipose tissue transcriptomic signature highlights the pathological relevance of extracellular matrix in human obesity

    Henegar, Corneliu / Arnaud Basdevant / Christine Poitou / Danièle Lacasa / Dominique Langin / Isabelle Cremer / Jean-Daniel Zucker / Joan Tordjman / Karine Clement / Michèle Guerre-Millo / Nathalie Viguerie / Pierre Bedossa / Vincent Achard / Vladimir Stich

    Genome biology. 2008 Sept., v. 9, no. 1

    2008  

    Abstract: BACKGROUND: Investigations performed in mice and humans have acknowledged obesity as a low-grade inflammatory disease. Several molecular mechanisms have been convincingly shown to be involved in activating inflammatory processes and altering cell ... ...

    Abstract BACKGROUND: Investigations performed in mice and humans have acknowledged obesity as a low-grade inflammatory disease. Several molecular mechanisms have been convincingly shown to be involved in activating inflammatory processes and altering cell composition in white adipose tissue (WAT). However, the overall importance of these alterations, and their long-term impact on the metabolic functions of the WAT and on its morphology, remain unclear. RESULTS: Here, we analyzed the transcriptomic signature of the subcutaneous WAT in obese human subjects, in stable weight conditions and after weight loss following bariatric surgery. An original integrative functional genomics approach was applied to quantify relations between relevant structural and functional themes annotating differentially expressed genes in order to construct a comprehensive map of transcriptional interactions defining the obese WAT. These analyses highlighted a significant up-regulation of genes and biological themes related to extracellular matrix (ECM) constituents, including members of the integrin family, and suggested that these elements could play a major mediating role in a chain of interactions that connect local inflammatory phenomena to the alteration of WAT metabolic functions in obese subjects. Tissue and cellular investigations, driven by the analysis of transcriptional interactions, revealed an increased amount of interstitial fibrosis in obese WAT, associated with an infiltration of different types of inflammatory cells, and suggest that phenotypic alterations of human pre-adipocytes, induced by a pro-inflammatory environment, may lead to an excessive synthesis of ECM components. CONCLUSION: This study opens new perspectives in understanding the biology of human WAT and its pathologic changes indicative of tissue deterioration associated with the development of obesity.
    Keywords bariatric surgery ; extracellular matrix ; fibrosis ; gene expression ; gene expression regulation ; genes ; genomics ; humans ; integrins ; long term effects ; mice ; obesity ; phenotype ; transcription (genetics) ; transcriptomics ; weight loss ; white adipose tissue
    Language English
    Dates of publication 2008-09
    Size p. 1876.
    Publishing place Springer-Verlag
    Document type Article
    ZDB-ID 2040529-7
    ISSN 1474-760X ; 1465-6914 ; 1465-6906
    ISSN (online) 1474-760X ; 1465-6914
    ISSN 1465-6906
    DOI 10.1186/gb-2008-9-1-r14
    Database NAL-Catalogue (AGRICOLA)

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