Granulocyte neutrophile

Résumé

Les granulocytes neutrophiles ou polynucléaires neutrophiles (PNN) (ou simplement « les neutrophiles ») sont des cellules sanguines appartenant à la lignée blanche. Ce sont des globules blancs (leucocytes) qui ont un rôle majeur dans le système immunitaire. Les neutrophiles font partie des cellules granulocytes ou « cellules polynucléaires ». On les appelle polynucléaires en raison d'une erreur historique : de par le caractère plurilobé de leur noyau (de deux à cinq lobes en général), on a longtemps cru que ces cellules possédaient plusieurs noyaux. Les autres granulocytes sont les granulocytes éosinophiles et basophiles. Le qualificatif de « neutrophile » vient aussi d'une caractéristique visible en microscopie optique : après ajout des colorants vitaux usuels (May-Grünwald Giemsa ou MGG), ces cellules restent neutres (elles fixent mal les colorants acides et basiques). Les neutrophiles représentent à eux seuls environ 65 % de l'ensemble des leucocytes du sang, et 99 % des granu

Source officielle

https://fr.wikipedia.org/wiki/Granulocyte_neutrophile

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vignette|Un lymphocyte, principale composante du système immunitaire adaptatif des vertébrés. Le système immunitaire d'un organisme est un système biologique complexe constitué d'un ensemble coordonn

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Les leucocytes (du grec leukos : blanc et kutos : cellule) ou globules blancs sont des cellules produites dans la moelle osseuse et présentes dans le sang, la lymphe, les organes lymphoïdes (ganglion

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The role of Snail in non-small cell lung cancer

Svenja Johanna Groeneveld

The epithelial-to-mesenchymal transition (EMT) is a developmental program frequently reactivated in cancer. It plays an important role in several aspects of tumor progression, particularly in the acquisition of invasive capacities facilitating metastasis. Beyond invasion, EMT endows cancer cells with additional characteristics essential for metastatic dissemination and has been extensively studied in breast and colorectal cancer. Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related deaths worldwide and the majority of NSCLC patients is diagnosed with metastatic disease. The expression of the key EMT transcription factor Snail is correlated with a poor prognosis in NSCLC patients, while it is unclear whether Snail contributes to disease progression by actually facilitating metastasis formation. During EMT, the metabolism of a cancer cell changes, likely to meet the environmental challenges faced during the metastatic process. In this line, we have previously reported (Masin et al, 2014) that the glucose transporter GLUT3 is upregulated during EMT in human NSCLC cell lines. Here, we demonstrate that the rate-limiting enzyme of the hexosamine biosynthesis pathway (HBP) correlates with GLUT3 in NSCLC. This pathway produces a substrate for O-linked protein GlcNAcylations important during EMT, as they â for example â stabilize the Snail protein. Glutamine-fructose-6-phosphate amidotransferase 2 (GFPT2) was specifically upregulated during EMT, while its isoenzyme GFPT1 was unaffected. Furthermore, our results points towards a putative regulation of GLUT3 expression by GFPT2, possibly involving STAT3 signaling. We thus provide evidence for a possible reactivation of a developmental metabolic program during EMT in NSCLC. Chronic inflammation is an important disease-promoting factor during lung tumorigenesis, emphasizing the role of the immune system in this cancer type. Overexpressing or silencing Snail in the immunocompetent autochthonous KrasLSL-G12D/+;p53fl/fl mouse model of lung adenocarcinoma uncovered a substantial influence of Snail on the tumor microenvironment. An extensive analysis of tumor histology, gene and protein expression and immune infiltration revealed that while Snail did not contribute to metastasis formation, it accelerated growth and malignant progression of the lung tumors, reducing the survival time of the mice. Snail decreased B lymphocyte, while enhancing neutrophil infiltration of the tumors. Intriguingly, through the secretion of a soluble factor, Snail induced a feed-forward loop of neutrophil recruitment via Cxcl2, produced by neutrophils themselves. In our recently published collaborative work (Faget, Groeneveld et al, 2017), we identified neutrophils as main contributors to disease progression. We furthermore provided evidence for a vicious cycle formed between Snail expressing cancer cells and neutrophils in lung tumors, as neutrophils were found to impair angiogenesis, resulting in hypoxia and enhanced Snail expression. In addition, we found that Snail repressed the Dlk1-Dio3 locus, containing the genomeâs largest miRNA cluster and recently implicated in NSCLC, in tumor-infiltrating immune cells via a paracrine mechanism.

EPFL2018

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Durable and controlled depletion of neutrophils in mice

Pierre-Benoit Bernard Ancey, Gael Luis Boivin, Caroline Anne-Lyse Contat, Julien Robert Rémi Faget, Aspasia Gkasti, Etienne Meylan, Justine Pascual, Jessica Christine Vazquez

Neutrophils are an essential part of the innate immune system. To study their importance, experimental studies often aim to deplete these cells, generally by injecting anti-Ly6G or anti-Gr1 antibodies. However, these approaches are only partially effective, transient or lack specificity. Here we report that neutrophils remaining after anti-Ly6G treatment are newly derived from the bone marrow, instead of depletion escapees. Mechanistically, newly generated, circulating neutrophils have lower Ly6G membrane expression, and consequently reduced targets for anti-Ly6G-mediated depletion. To overcome this limitation, we develop a double antibody-based depletion strategy that enhances neutrophil elimination by anti-Ly6G treatment. This approach achieves specific, durable and controlled reduction of neutrophils in vivo, and may be suitable for studying neutrophil function in experimental models.

2020

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High T-cell infiltration in colorectal cancer (CRC) correlates with a favorable disease outcome and immunotherapy response. This, however, is only observed in a small subset of CRC patients. A better understanding of the factors influencing tumor T-cell responses in CRC could inspire novel therapeutic approaches to achieve broader immunotherapy responsiveness. Here, we investigated T cell-suppressive properties of different myeloid cell types in an inducible colon tumor mouse model. The most potent inhibitors of T-cell activity were tumor-infiltrating neutrophils. Gene expression analysis and combined in vitro and in vivo tests indicated that T-cell suppression is mediated by neutrophil-secreted metalloproteinase activation of latent TGF beta. CRC patient neutrophils similarly suppressed T cells via TGF beta in vitro, and public gene expression datasets suggested that T-cell activity is lowest in CRCs with combined neutrophil infiltration and TGF beta activation. Thus, the interaction of neutrophils with a TGF beta-rich tumor microenvironment may represent a conserved immunosuppressive mechanism in CRC.

WILEY2020

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The role of Snail in non-small cell lung cancer

Svenja Johanna Groeneveld

EPFL2018