Immunité et cancers des voies aéro-digestives supérieures 2

Les cellules immunitaires engendrent des réponses anti-tumorales en reconnaissant les antigènes spécifiques des tumeurs. Un échec du contrôle immunitaire est le plus souvent observé. Ceci est à l’origine de travaux de recherche dont l’objectif est de concevoir l’immunothérapie des cancers. Le meilleur exemple est le développement des anticorps monoclonaux (thérapie ciblée), qui sont une avancée majeure dans le traitement des cancers. Le traitement des cancers des VADS (Voies Aéro-Digestives Supérieures) reste conventionnel, utilisant chirurgie, radiothérapie et chimiothérapie classique. L’objectif de ce travail est une mise au point sur les espoirs de l’immunothérapie dans le traitement des cancers des VADS

Immunité et cancers des voies aéro-digestives supérieures 1

Les cancers des voies aéro-digestives supérieures (VADS) sont un problème de santé publique majeur. Chez l’homme, ces cancers arrivent en troisième place en termes de fréquence en France. Le pronostic est sombre, la survie des patients ne dépasse pas 20 % à 10 ans. Il est nécessaire de s’intéresser à l’environnement tumoral, afin de mieux comprendre les étapes de formation et d’extension, ainsi que les interactions avec le système immunitaire de l’hôte. L’identification de nouveaux biomarqueurs, témoins du processus cancéreux mais aussi d’une éventuelle réponse immunitaire anti-tumorale pourraient constituer des éléments du diagnostic et du pronostic, mais aussi des cibles thérapeutiques. Cette revue de la littérature a pour but de faire le point sur la réponse immunitaire et l’échappement tumoral des cancers des VADS

A first experience of transduction for differentiated HepaRG cells using lentiviral technology

International audienceCurrently, there is a lack of systems for studying the role of hepatitis B viral proteins, such as HBeAg and HBcAg, on liver injury. It is necessary to develop an original tool in order to clarify the role of these viral proteins in hepatic stellate cell activation, and to understand the molecular mechanisms of liver injury. HepaRG are the most reliable hepatocyte-like cells for studying liver functions or disorders. In this paper, we demonstrate that the transduction of differentiated HepaRG (dHepaRG) cells can be performed successfully using lentiviral particles. The production of a functional Green Fluorescent Protein (GFP) assessed by Fluorescence Activated Cell Sorting and fluorescence microscopy is up to 16% of GFP positive cells using a multiplicity of infection (MOI) of 2.4. We demonstrate that this technology can allow the stable expression of GFP during the long lifecycle of the cell (up to four weeks after the cell’s passage). With this innovative tool, we aim to express viral proteins such as HBeAg or HBcAg in dHepaRG cells. The preliminary results of this work shows that HBeAg can be efficiently produced in dHepaRG cells and that increased MOI allows a better production of this protein. Our future objective will be to study the role of HBc and HBe proteins on the induction of hepatic fibrosis

Cigarette smoking induces human CCR6+Th17 lymphocytes senescence and VEGF-A secretion

International audienceChronic exposure to environmental pollutants is often associated with systemic inflammation. As such, cigarette smoking contributes to inflammation and lung diseases by inducing senescence of pulmonary cells such as pneumocytes, fibroblasts, and endothelial cells. Yet, how smoking worsens evolution of chronic inflammatory disorders associated with Th17 lymphocytes, such as rheumatoid arthritis, psoriasis, Crohn's disease, and multiple sclerosis, is largely unknown. Results from human studies show an increase in inflammatory CD4+ Th17 lymphocytes at blood- and pulmonary level in smokers. The aim of the study was to evaluate the sensitivity of CD4+ Th17 lymphocytes to cigarette smoke-induced senescence. Mucosa-homing CCR6+ Th17- were compared to CCR6neg -and regulatory T peripheral lymphocytes after exposure to cigarette smoke extract (CSE). Senescence sensitivity of CSE-exposed cells was assessed by determination of various senescence biomarkers (β-galactosidase activity, p16Ink4a- and p21 expression) and cytokines production. CCR6+ Th17 cells showed a higher sensitivity to CSE-induced senescence compared to controls, which is associated to oxidative stress and higher VEGFα secretion. Pharmacological targeting of ROS- and ERK1/2 signalling pathways prevented CSE-induced senescence of CCR6+Th17 lymphocytes as well as VEGFα secretion. Altogether, these results identify mechanisms by which pro-oxidant environmental pollutants contribute to pro-angiogenic and pathogenic CCR6+Th17 cells, therefore potential targets for therapeutic purposes

GFP-transduced CD34+ and Lin- CD34- hematopoietic stem cells did not adopt a cardiac phenotype in a nonhuman primate model of myocardial infarct.

International audienceOBJECTIVE: Studies in mice have reported contradictory results on the contribution of bone marrow cells to myocardial regeneration. This study aims to evaluate their ability to differentiate into cells of cardiac lineage in a nonhuman primate mode of myocardial infarct. MATERIALS AND METHODS: Lin(-)CD34(-) and CD34(+)-enriched bone marrow cells or mobilized peripheral blood cells were transduced with green fluorescent protein (GFP) and injected directly into ischemic myocardium. The fate of the transplanted cells was evaluated using quantitative reverse transcription polymerase chain reaction (QRT-PCR) and immunohistology. Animals were followed-up using echocardiography. RESULTS: QRT-PCR analysis detected from 3% to 10% of the original number of administered GFP(+) cells after 7 days. These GFP(+) cells did not express cardiac tissue-specific markers, but were immunophenotypically consistent with undifferentiated hematopoietic cells. The local production of vascular endothelial growth factor, measured by QRT-PCR, was approximately doubled as compared to the untreated infarcted control heart. Three months after hematopoietic stem cell (HSC) administration, no GFP(+) cells were detected and no evidence of regeneration of the infarcted region was found by histological examination. In contrast, a high level of matrix metalloproteinase 2 was measured in infarct and peri-infarct area. At this time, an improved ejection fraction and decreased left ventricular chamber dimension, which might be also related to a natural course after reperfusion, were observed. CONCLUSIONS: Our data show that GFP(+) CD34(+) and Lin(-)CD34(-)-enriched HSC do not differentiate into cardiomyocytes or into endothelial cells in the infarcted myocardium and that the local production of some growth factors had no positive effect on myocardial regeneration after 3 months