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Séminaires & conférences

    

 

Friday, March 13, 11h30

Gustave Roussy Amphitheatre

 

SEMINAIRE ANNULE

 

 Solid tumours :

the new challenge for the immunotherapy

Ignazio CARUANA

Bambino Gesu children's hospital, Roma, Italy

  Invited by Elena Carcarino and Fawaz Alzaid

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Summary :

Substantial progress has been made in the treatment of solid tumours over the past decades. However, in particular children with high-risk, metastatic or relapsed disease continue to have a poor prognosis despite the aggressive multi-modal conventional therapies, which are associated with significant toxicity leading to long-term morbidity and an increased secondary malignancy rate. Furthermore, it is extremely important to underline that these patients often become refractory to therapy. For this reason, there is a great need to develop alternative anticancer therapies, which are less toxic and more effective. The increasing understanding of tumour biology and the interaction between the tumour and the immune system over the recent years have led to the development of novel immune-based therapies in which the patient’s own immune system is mobilized to fight the cancer in a specific way, thereby causing only mild toxicity. Several solid tumours appear to be susceptible to these immunotherapies, which include monoclonal antibodies, T cell immune responses and oncolytic therapies. Importantly, resistance to conventional therapies does not appear to confer resistance to immune-based therapies. To combine the beneficial effects of both humoral and cell-mediated components of the anti-tumour response, T lymphocytes can be genetically modified to express chimeric proteins known as chimeric antigen receptors (CARs) that combine the antigen-binding specificity of a monoclonal antibody with the effector endodomain of the CD3/T cell receptor complex (z chain). Whereas dramatic anti-tumour potency is observed in patients with B-cell malignancies treated with CD19-specific CAR T cells, such as acute lymphoblastic leukaemia and non–Hodgkin lymphomas, challenges to achieve similar responses in patients harbouring solid tumours are considerable. Indeed, although there are clinical trials using CAR T cells in solid tumours, clinical results are still negligible. This can be easily explained by the different nature of these tumours with particular reference to the tumour microenvironment and mechanisms to block and/or circumvent immune responses.

In this presentation, using neuroblastoma and gliomas as models, I will depict several mechanisms that we developed to overcome the limited efficacy of advanced immunotherapies such as CAR-T cell and oncolytic adenovirus immunotherapy

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Friday, March 20, 11h30

Gustave Roussy Amphitheatre

 

 The imprinted DLK1/DIO3 locus as  a key player

in beta-catenin driven  tumorigenesis

 

Julie SANCEAU

CRC, Lab. Sabine Colnot

  Invited by Guilhem Lignon and Angélique Gougelet

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Summary :

Hepatocellular carcinoma (HCC) is the second leading cause of death related to cancer worlwide. In b-catenin mutated HCC (30% of HCC), we discovered that the imprinted DLK1-DIO3 locus was globally overactivated, in both mouse and human tumors. This locus contains the bigest cluster of ncRNAs and we aim to determine whether its mIRNAs could be promising therapeutic target. We used a transgenic, inducible, mouse model with a hepotospecific inactivation of Apc, which leads to an abnormal activation of b-catenin pathway (Apc). ChIP-seq analysis allows us to identify a site of b-catenin fixation upstream of the locus on two WREs (wnt responsive element) leading to chromatin opining (ATAC-seq), intragenic hypermethylation (MeDIP-seq) and locus induction (RNA-seq) in Apc hepatocytes. Demethylating agent decreases DLK1-DIO3 RNAs expression in Apc hepatocyte. We also observed, in co-culture, the existence of a dialogue between hepatocytes and non-parenchymal cells (NPC) for the locus, NPCs from a Apc microenvironment being able to activate the locus in wild type hepatocytes by direct contact and secreting factors. Therefore, we used the CRISPR-Cas9 technology to inactivate the DLK1-DIO3 locus expression by removing the b-catenin fixation site upstream of the locus. Using murine HCC cells, we observed a significant decrease in AWRE cell proliferation in vitro, and in tumor growth in vivo in allografts on athymic mouse, associated with a decreased of proliferative cell (Ki67) and an increase of apoptotic cell (Caspase 3). Using AAV8 particles in vivo in Apc mice, we observed a decrease in the expression of DLK1-DIO3 RNAs in Apc hepatocyte with a sharp decrease in cell proliferation and a remodeling of microenvironment Altogether, the locus seems to be a dey driver of b-catenin dependent HCC tumorigenesis and could be a very promising therapeutic target.

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Friday, March 27, 11h30

Gustave Roussy Amphitheatre

 

SEMINAIRE ANNULE

 

Quantifying the evolutionary dynamics

of human cancers

Trevor GRAHAM

Barts Cancer Institute, QMUL, London, UK

  Invited by Jessica Zucman-Rossi and Angélique Gougelet

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Summary :

The fundamental evolutionary parameters that define cancer evolution, such as the mutation rate per cell division and selective advantage conferred by each mutation, remain poorly characterised. Here I will discuss how these parameters can be derived from routinely-available cancer genome sequencing data, via statistical inference of mathematical population genetics models of clonal evolution. We measure that positively selected mutations can cause fitness increases as large as 50%, and also explore the dynamics of negatively-selected mutations (neoantigens) in a growing tumour. These quantitative measurements of cancer evolution enable mechanistic forecasting of the future evolution of a tumour.

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Tuesday, March 31, 14h00-17h00

Bilsky-Pasquier Amphitheatre

 

 Mini-Symposium @CRC : 

 Single Cell and Epigenetics

 

  Organized by Jessica Zucman-Rossi and Angélique Gougelet

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Program coming soon

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Friday, April 3, 11h30

Gustave Roussy Amphitheatre

 

 Canonical and novel roles of class 3 PI3K

signaling in metabolic control

Ganna PANASYUK

Inserm U1151/CNRS UMR 8253, Inem, Paris

  Invited by Jessica Zucman-Rossi and Fabienne Foufelle

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Summary :

Ganna Panasyuk is a head of the team 17 at Necker Institute of Sick Children (INSERM Unit 1151, Paris, France). She has earned her PhD degree in Molecular Biology from the Institute of Molecular biology and Genetics in Kyiv, Ukraine. Early on in her training she has got interested in transduction mechanisms governing growth control such as mTOR/PI3K signalling pathway. She was trained in this field as a postdoc, first, in the lab of Ivan Gout at University College London, UK, and then in the lab of Mario Pende at INSERM, Paris, France. Since 2013 she holds a senior scientist tenure track position at INSERM and in 2019 was awarded research director position to lead the research program at INEM institute. Today, her team aims to elucidate molecular mechanisms of metabolic control and its implication in human disease. Ganna’s team zooms-in into different facets of PI3K signalling. For this seminar, she will briefly present a recently published story of her team (Iershov et al., Nature Comm 2019) and an on-going work about unappreciated metabolic roles of largely enigmatic class 3 PI3K signalling. To learn more about Ganna Panasyuk team go to: http://www.panasyuklab.fr

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Friday, April 10, 11h30

Gustave Roussy Amphitheatre

 

 Therapeutic monoclonal antibodies in oncology :

issues and developments

Charles DUMONTET

Centre de recherche en cancérologie - Lyon

  Invited by EATI (Guido Kroëmer and Jonathan Pol)

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Summary :

Coming soon

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Friday, April 17, 11h30

Gustave Roussy Amphitheatre

 

 TD-Nuclear Magnetic Resonance to visualize

 water, fat, and lean masses in mice

 

Luciana MORLA

CRC, Lab. Gilles CRAMBERT

  Invited by Guilhem Lignon and Angélique Gougelet

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Summary :

Maintaining water homeostasis is fundamental for cellular function. Many diseases and drugs affect water balance and plasma osmolality. Water homeostasis studies in small animals require the use of invasive or terminal methods that make intracellular and extracellular fluid volume (ICF and ECF) monitoring over time stressful and time consuming. We examined the feasibility of monitoring mice ECF by a non‐invasive method, using time‐domain nuclear magnetic resonance (TD‐NMR). This technique allows differentiating protons in a liquid environment (free fluid) from protons in soft tissues containing a majority of either small molecules (lean) or large molecules (fat). Moreover, this apparatus enables rapid, non‐invasive, and repeated measurements on the same animal. We assessed the feasibility of coupling TD‐NMR analysis to a longitudinal metabolic cage study by monitoring mice daily.  We determined the effect of a 24‐hour water deprivation on mice body parameters and detected a sequential and overlapping decrease in free fluid and lean mass during water deprivation. Finally, we studied the effect of mineralocorticoids that are known to induce a transient increase in the ECF but for which no direct measurements have been performed in mice. We show for the first time that mineralocorticoids induce a transient ~20 % increase in free fluid in conscious mice. TD‐NMR is therefore the first method to allow direct measurement of discrete changes in the ECF in conscious small animals. This method allows analysis of kinetic changes to stimuli prior to investigating with terminal methods and will allow further understanding of fluid disorders. We will also discuss changes in fat mass and lean during the day and important aspects to take in account when using this tool.

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Friday, April 24, 11h30

Gustave Roussy Amphitheatre

                       
               SEMINAIRE ANNULE

Andreas MACKENSEN

Universitätsklinikum Erlangen, Germany

  Invited by EATI (Guido Kroëmer and Jonathan Pol)

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Summary :

Coming soon

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Friday, May 15, 11h30

Gustave Roussy Amphitheatre

 

 Title to come

Elizabeth JAFFEE

Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, USA

  Invited by EATI (Guido Kroëmer and Jonathan Pol)

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Summary :

coming soon

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Friday, May 29, 11h30

Gustave Roussy Amphitheatre

 

 Title to come

Federico MINGOZZI

Sparks Therapeutics, USA

  Invited by Jessica Zucman-Rossi and Sébastien Lacroix-Desmazes

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Summary :

Coming soon

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Friday, June 5, 11h30

Gustave Roussy Amphitheatre

 

 Title to come

Laurent YVAN-CHARVET

C3M, Nice

  Invited by Jessica Zucman-Rossi, Chantal Desdouets, Nicolas Venteclef

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Summary :

Coming soon

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Friday, June 12, 11h30

Gustave Roussy Amphitheatre

 

 Title to come

Elena CARCARINO

CRC, Lab. Nicolas VENTECLEF

  Invited by Guilhem Lignon and Angélique Gougelet

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Summary :

Coming soon

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Friday, June 19, 11h30

Gustave Roussy Amphitheatre

 

 Heme as a modulator of the therapeutic

efficacy of anti-cancer antibodies

Alexia TAVARES KANYAVUZ

CRC, Lab. Sébastien LACROIX-DESMAZES

Invited by Guilhem Lignon and Angélique Gougelet

  

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Summary :

Polyreactive antibodies are able to bind multiple structurally unrelated antigens with similar values of binding affinity. Besides natural polyreactive antibodies, some monoreactive antibodies can acquire polyreactivity post-translationally by interaction with low molecular weight substances such as heme. Although the molecular mechanism and biological functions of induced polyreactive antibodies are still not well understood, some investigations have shown that these antibodies are involved in different physiopathological processes. Importantly, McIntyre et al. have reported that 9 therapeutic monoclonal antibodies that are currently used in clinical practice can acquire autoreactivity upon exposure to heme. Several of these antibodies are used in the cancer therapy, as Rituximab (anti-CD20 chimeric antibody) for the treatment of B-cell non-Hodgkin’s lymphoma and Trastuzumab (anti-HER2 humanized antibody) for the treatment of certain forms of breast cancer. The cell damage that accompanies cancer therapy or certain pathological conditions can result in the release of redox-active compounds, including heme, and could lead to uncover the cryptic polyreactivity of these therapeutic antibodies in vivo. The aim of my PhD project was to understand how heme affects the functional activity and the therapeutic potential of these therapeutic antibodies.

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AND 

 Title to come

Mickaël MENAGER

Institut Imagine, Paris

 

Invited by Guilhem Lignon and Angélique Gougelet

  

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Summary :

Coming soon

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Friday, July 3, 11h30

Gustave Roussy Amphitheatre

 

 Title to come

Catherine BLANC and Aurélien CORNEAU

CyPS, Pitié-Salpêtrière, Paris

  Invited by Chiara MAIURI

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Summary :

Coming soon

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Friday, September 11, 11h30

Gustave Roussy Amphitheatre

 

 Vasopressin and cardiometabolic disease,

is water a new prevention strategy ?

Olle MELANDER

Lund University and Skane University Hospital, Sweden

  Invited by Jessica Zucman-Rossi and Gilles Crambert

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SUMMARY :

Vasopressin (VP), commonly proxie-measured with a stable C-terminal fragment of the precursor hormone called copeptin, is elevated not only in cases of acute diseases with severe water losses (e.g. gastroenteritis) or hypotension (e.g. septic shock) but also in normal states when water intake is low. This preserves normal plasma osmolality thanks to renal water conservation through VP stimulation of the V2-receptor. However, as will be demonstrated in this talk, high levels of copeptin in the population is linked to markedly increased risk of type 2 diabetes mellitus, cardiovascular disease and chronic kidney disease, independently of other risk factors. Moreover, obese individuals with high copeptin are at increased risk of Non-Alcoholic Fatty Liver Disease (NAFLD). A challenging question based on the hypothesis that high VP (measured by copeptin) is causally related to these diseases, is whether the elevation of cardiometabolic risk in normal subjects with high VP and other signs of low water intake (low urine volume and high urine osmolality) can be reversed by water supplementation. Data from animals and humans to support this hypothesis will be presented. 

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Friday, October 2, 11h30

Gustave Roussy Amphitheatre

 

 Title to come

Christophe ROUSSELLE

ANSES, Maisons-Alfort

  Invited by Jessica Zucman-Rossi and Sylvie Babajko

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Summary :

Coming soon 

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Friday, October 30, 11h30

Gustave Roussy Amphitheatre

 

 Title to come

Frédéric THOMAS

IRD, Marseille

  Invited by Jessica Zucman-Rossi and Angélique Gougelet

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Summary :

Coming soon 

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Friday, November 13, 11h30

Gustave Roussy Amphitheatre

 

Quantifying the evolutionary dynamics

of human cancers

Trevor GRAHAM

Barts Cancer Institute, QMUL, London, UK

  Invited by Jessica Zucman-Rossi and Angélique Gougelet

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Summary :

The fundamental evolutionary parameters that define cancer evolution, such as the mutation rate per cell division and selective advantage conferred by each mutation, remain poorly characterised. Here I will discuss how these parameters can be derived from routinely-available cancer genome sequencing data, via statistical inference of mathematical population genetics models of clonal evolution. We measure that positively selected mutations can cause fitness increases as large as 50%, and also explore the dynamics of negatively-selected mutations (neoantigens) in a growing tumour. These quantitative measurements of cancer evolution enable mechanistic forecasting of the future evolution of a tumour.

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