Mesenchymal Stem cells from human lung squamous cell carcinoma modulate NK phenotype and function

Mesenchymal stem cells (MSCs) display pleiotropic functions, which include secretion of soluble factors with immunosuppressive activity implicated in cancer progression. We compared the immunomodulatory effects of paired intra-tumor (T-) and adjacent non-tumor tissue (N-)- derived MSCs from patients with squamous cell lung carcinoma (SCC) on circulating natural killer (NK) cells from healthy donors. We observed that T-MSCs were more strongly immunosuppressive than N-MSCs and affected both NK function and phenotype, as defined by CD56 expression. T-MSCs shifted NK cells toward the CD56dim phenotype and differentially modulated CD56bright/dim subset functions. Whereas MSCs affected both degranulation and expression of activating receptors in the CD56dim subset, they primarily inhibited interferon- production in the CD56bright subset. Pharmacological inhibition of prostaglandin E2 (PGE2) synthesis, and in some MSCs, IL-6 activity, restored NK function, whereas NK cell stimulation by PGE2 alone mimicked T-MSC-mediated immunosuppression. Our observations provide insight into how stromal responses to cancer dampen NK cell activity in human lung SCC. -- Les cellules mésenchymateuses souches (CMS) sont des cellules du stroma (tissu de soutien), avec des fonctions multiples, dont des propriétés immunosuppressives impliquées dans la progression tumorale et nécessitant la sécrétion de facteurs solubles. Dans ce travail, nous avons comparé les effets immunomodulatoires de CMS humaines isolées de pièces de résection de cancer pulmonaire épidermoïde (T-CMS), avec ceux de CMS issues du tissu pulmonaire non tumoral adjacent (N-CMS), prélevé chez les mêmes patients. Nous nous sommes intéressés à l’effet des CMS sur l’immunité innée, en particulier sur les cellules tueuses naturelles (NK). Nous avons observé que les T-CMS sont plus immunosuppressives que les N-CMS et affectent aussi bien la fonction que le phénotype des NK, y compris leur expression du CD56. Les T-CMS induisent préférentiellement des NK CD56dim, et ont des effets différents sur les fonctions des sous-populations CD56dim et CD56bright. Les CMS affectent à la fois la degranulation et l’expression des récepteurs activateurs des CD56dim, alors qu’elles inhibent principalement la sécrétion d’IFN-dans la sous-population CD56bright. L’inhibition pharmacologique de la synthèse de la prostaglandine E2 (PGE2), et pour certaines CMS, de l’activité de l’IL-6, est capable de restaurer la fonction des NK, alors que la stimulation par la PGE2 seule reproduit l’effet suppresseur des T-CMS. Nos observations permettent une meilleure compréhension de la réponse stromale et de son caractère immunosuppresseur sur les NK dans le cancer pulmonaire chez l’homme

Sadržaj

Metastasis is a multi-step process in which direct crosstalk between cancer cells and their microenvironment plays a key role. Here, we assessed the effect of paired tumor-associated and normal lung tissue mesenchymal stem cells (MSCs) on the growth and dissemination of primary human lung carcinoma cells isolated from the same patients. We show that the tumor microenvironment modulates MSC gene expression and identify a four-gene MSC signature that is functionally implicated in promoting metastasis. We also demonstrate that tumor-associated MSCs induce the expression of genes associated with an aggressive phenotype in primary lung cancer cells and selectively promote their dissemination rather than local growth. Our observations provide insight into mechanisms by which the stroma promotes lung cancer metastasis

Combination of Interdisciplinary Training in Space Technology with Project-Related Work through the CubeSat SOURCE

In April 2018, student work on the first satellite mission primarily dedicated to education at the IRS, SOURCE (Stuttgart Operated University Research CubeSat for Evaluation and Education) began. The phase A study resulted in a three-unit CubeSat design and a cooperation with a variety of industrial partners. Besides its educational purpose, the mission features technological and scientific objectives, the latter of which concentrate on the field of re-entry research. With the current status of the project, a large number of students have been introduced to and trained in all aspects of a satellite mission, like management, project sequences, concurrent engineering, space industry standards, and the application of specialized technical knowledge. This paper gives an overview of the CubeSat SOURCE and its educational approaches

Saint-Julien-lès-Metz (Moselle) « Ferme de Grimont » : Site d'habitat Groβgartach/épi-Roëssen : rapport de fouilles

Le site de Saint-Julien constitue un ensemble exceptionnel pour le Néolithique moyen en Lorraine. Implanté en rebord de plateau, le site décapé sur une superficie de 4822m2 se caractérise par la présence de deux habitations distantes d’environ quarante mètres, d’une grande fosse d’extraction, d’une structure de combustion et d’une structure de conservation de type silo. La grande fosse polylobée de 200m2 est isolée des maisons, elle a livré un mobilier abondant qui se rattache au GroLe site de Saint-Julien constitue un ensemble exceptionnel pour le Néolithique moyen en Lorraine. Implanté en rebord de plateau, le site décapé sur une superficie de 4822m2 se caractérise par la présence de deux habitations distantes d’environ quarante mètres, d’une grande fosse d’extraction, d’une structure de combustion et d’une structure de conservation de type silo. La grande fosse polylobée de 200m2 est isolée des maisons, elle a livré un mobilier abondant qui se rattache au Groβgartach et à l’épi-Rössen

Lupus anticoagulant-hypoprothrombinemia syndrome and catastrophic antiphospholipid syndrome in a patient with antidomain I antibodies

International audienceLupus anticoagulant-hypoprothrombinemia syndrome is a rare condition characterized by the association of acquired factor II deficiency and lupus anticoagulant. Contrary to classical antiphospholipid syndrome, it may cause severe life-threatening bleeding (89% of published cases). We report a patient, positive for antidomain I antibodies, with initially primary lupus anticoagulant-hypoprothrombinemia syndrome without previous clinical manifestation or underlying systemic disease. Five years later, he experienced the first systemic lupus erythematous flare. Within a few days, catastrophic antiphospholipid syndrome was diagnosed with heart, liver and kidney involvement. The patient recovered under pulse steroids, intravenous heparin and intravenous immunoglobulins

Title: AA amyloidosis complicating monoclonal gammopathies, an unusual feature validating the concept of "monoclonal gammopathy of inflammatory significance"? Authors: Alexandre Terré¹ , ¹³ https://orcid.org/0000-0002-8295-9068, Magali Colombat²

International audienceIntroductionAL amyloidosis is caused by the proliferation of an immunoglobulin-secreting B cell clone. AA amyloidosis is a rare complication of chronic inflammation. However, some patients present with diseases combining monoclonal immunoglobulin production and chronic inflammation. The aim of this work was to describe cases of AA amyloidosis associated with monoclonal gammopathies.Patients and methodsWe reviewed all patients reported in French national amyloid centres presenting with AA amyloidosis and monoclonal gammopathy and performed a literature review. The quality of AA amyloidosis diagnosis and the causal relationship with monoclonal gammopathy were assessed.ResultsIn total, four patients from our centres and eight from the literature fulfilled the inclusion criteria. The haematological disorders presenting with monoclonal gammopathy were as follows: Waldenström macroglobulinaemia (n = 8), Schnitzler syndrome (n = 2), multiple myeloma (n = 1) and monoclonal gammopathy of undetermined significance (n = 1). Treatment strategies varied among the cases, with the treatment of the haematological disorder in 4 and anti-inflammatory treatment in 2.ConclusionMonoclonal gammopathies might be a rare and poorly known cause of AA amyloidosis. Such monoclonal gammopathies could be named “monoclonal gammopathies of inflammatory significance.