61 research outputs found
Single-cell transcriptomics reveals shared immunosuppressive landscapes of mouse and human neuroblastoma
BACKGROUND
High-risk neuroblastoma is a pediatric cancer with still a dismal prognosis, despite multimodal and intensive therapies. Tumor microenvironment represents a key component of the tumor ecosystem the complexity of which has to be accurately understood to define selective targeting opportunities, including immune-based therapies.
METHODS
We combined various approaches including single-cell transcriptomics to dissect the tumor microenvironment of both a transgenic mouse neuroblastoma model and a cohort of 10 biopsies from neuroblastoma patients, either at diagnosis or at relapse. Features of related cells were validated by multicolor flow cytometry and functional assays.
RESULTS
We show that the immune microenvironment of MYCN-driven mouse neuroblastoma is characterized by a low content of T cells, several phenotypes of macrophages and a population of cells expressing signatures of myeloid-derived suppressor cells (MDSCs) that are molecularly distinct from the various macrophage subsets. We document two cancer-associated fibroblasts (CAFs) subsets, one of which corresponding to CAF-S1, known to have immunosuppressive functions. Our data unravel a complex content in myeloid cells in patient tumors and further document a striking correspondence of the microenvironment populations between both mouse and human tumors. We show that mouse intratumor T cells exhibit increased expression of inhibitory receptors at the protein level. Consistently, T cells from patients are characterized by features of exhaustion, expressing inhibitory receptors and showing low expression of effector cytokines. We further functionally demonstrate that MDSCs isolated from mouse neuroblastoma have immunosuppressive properties, impairing the proliferation of T lymphocytes.
CONCLUSIONS
Our study demonstrates that neuroblastoma tumors have an immunocompromised microenvironment characterized by dysfunctional T cells and accumulation of immunosuppressive cells. Our work provides a new and precious data resource to better understand the neuroblastoma ecosystem and suggest novel therapeutic strategies, targeting both tumor cells and components of the microenvironment
Fostering responsible research with genome editing technologies : a European perspective
In this consensus paper resulting from a meeting that involved representatives from more than 20 European partners, we recommend the foundation of an expert group (European Steering Committee) to assess the potential benefits and draw-backs of genome editing (off-targets, mosaicisms, etc.), and to design risk matrices and scenarios for a responsible use of this promising technology. In addition, this European steering committee will contribute in promoting an open debate on societal aspects prior to a translation into national and international legislation.peer-reviewe
COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study
Background:
The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms.
Methods:
International, prospective observational study of 60â109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms.
Results:
âTypicalâ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (â€â18 years: 69, 48, 23; 85%), older adults (â„â70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each Pâ<â0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country.
Interpretation:
This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men
LâinterdisciplinaritĂ© sâinvite dans les systĂšmes complexes : les journĂ©es de Rochebrune
Trente chercheurs, de sciences sociales et de sciences de lâinformation, Ă©taient rĂ©unis
une semaine fin janvier 2014 pour les journées de Rochebrune, « rencontres
interdisciplinaires sur les systÚmes complexes naturels et artificiels », qui ont lieu
chaque année depuis 1992. Le thÚme choisi, « Multi-trans-interdisciplinarité », ouvrait
explicitement un bilan de ces journées. Nous retenons de ce bilan une série
dâinterrogations. Quels sont les liens qui se tissent entre les disciplines et quels sont
les objectifs de construction Ă plusieurs points de vue ? Comment valoriser les
différences de langages et de méthodes entre disciplines ? à quelles conditions les
modĂšles peuvent-ils intĂ©grer des connaissances hĂ©tĂ©rogĂšnes ? La recherche dâunification,
source dâinnovations et dâenrichissement, prĂ©sente Ă©galement les risques dâun lissage des
disciplines, dâune perte de spĂ©cificitĂ© du langage, et dâune domination par les sciences
de lâinformation. Ă la fois outil technique et cadre conceptuel, les systĂšmes complexes
apportent des entrĂ©es multiples pour la construction, lâintĂ©gration ou la confrontation
interdisciplinaire
Un CĂ©ratopogonide nouveau [Dipt.]
Harant Hervé, Cellier MylÚne. Un Cératopogonide nouveau [Dipt.]. In: Bulletin de la Société entomologique de France, volume 54 (1), janvier 1949. pp. 10-11
RĂ©silience, adaptation, changement : lâinterdisciplinaritĂ© questionnĂ©e
La troisiÚme conférence internationale du réseau Resilience Alliance « Résilience et
dĂ©veloppement : mobiliser pour la transformation », sâest tenue Ă Montpellier du 4 au
8Â mai 2014. Lâobjectif de cette manifestation Ă©tait de confronter les nombreuses approches
de la résilience autour du thÚme de la transformation. Nous analysons la place de
lâinterdisciplinaritĂ© dans cet important rassemblement. Quelles sont les mĂ©thodes mises en
place dans le travail entre disciplines ? Quels sont les questionnements et les défis
soulevés ? Quels concepts ou cadres théoriques se révÚlent innovants ? Les technologies de
lâinformation et lâoutillage maths-informatique apportent-ils des solutions ? Au fil de ce
compte rendu, nous montrons que lâinterdisciplinaritĂ© est finalement un enjeu important de
la « mobilisation pour la transformation », explicite dans le titre de la conférence, mais
que les dĂ©fis sont loin dâĂȘtre rĂ©solus
Jouer pour comprendre les enjeux de la concertation sur lâĂ©tablissement des Plans de PrĂ©vention des Risques Technologiques (PPRT)
Riskopolis est un jeu de rĂŽles que lâon peut classer dans la catĂ©gorie des serious games. Il possĂšde donc Ă la fois une dimension « ludique » et une dimension « éducative ». Son objet est de simuler une situation de concertation entre diffĂ©rents types dâusagers dans un contexte dâamĂ©nagement dâune ville industrielle. Il sâagit principalement de voir comment, par la nĂ©gociation, rendre compatibles des activitĂ©s de production Ă risque avec dâautres types de fonctions urbaines (habiter, produire..
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