SMAC mimetic drives microglia phenotype and glioblastoma immune microenvironment.

Tumor-associated macrophages/microglia (TAMs) are highly plastic and heterogeneous immune cells that can be immune-supportive or tumor-supportive depending of the microenvironment. TAMs are the most abundant immune cells in glioblastoma (GB), and play a key role in immunosuppression. Therefore, TAMs reprogramming toward immune-supportive cells is a promising strategy to overcome immunosuppression.

Three-Dimensional Imaging of Macrophages in Complete Organs.

The introduction of the light-sheet microscope has facilitated the analysis of complete tissues for the presence of all cells and their location in relation to their niche. This contributes to a better understanding of cellular locations and interactions in organs. In the last decade, many new and improved protocols have been published which are essential to improve staining and visualization of the immune-fluorescence within different tissues.

Brain endothelial CXCL12 attracts protective natural killer cells during ischemic stroke.

Background: The innate lymphoid cell (ILC) family consists of NK cells, ILC type 1, 2, 3 and lymphoid tissue inducer cells. They have been shown to play important roles in homeostasis and immune responses and are generally considered tissue resident. Not much is known about the presence of ILC members within the central nervous system and whether they are tissue resident in this organ too.

Distinct Waves from the Hemogenic Endothelium Give Rise to Layered Lymphoid Tissue Inducer Cell Ontogeny.

During embryogenesis, lymphoid tissue inducer (LTi) cells are essential for lymph node organogenesis. These cells are part of the innate lymphoid cell (ILC) family. Although their earliest embryonic hematopoietic origin is unclear, other innate immune cells have been shown to be derived from early hemogenic endothelium in the yolk sac as well as the aorta-gonad-mesonephros.

Deciphering the Crosstalk Between Myeloid-Derived Suppressor Cells and Regulatory T Cells in Pancreatic Ductal Adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is a fatal disease with rising incidence and a remarkable resistance to current therapies. The reasons for this therapeutic failure include the tumor's extensive infiltration by immunosuppressive cells such as myeloid-derived suppressor cells (MDSCs) and regulatory T cells (Tregs). By using light sheet fluorescent microscopy, we identified here direct interactions between these major immunoregulatory cells in PDAC.

Ribonuclease MCPiP1 contributes to the loss of micro-RNA-200 family members in pancreatic cancer cells.

The microRNA-200 (miR-200) family is frequently down-regulated in tumors, including pancreatic adenocarcinomas (PDACs). In this study we have examined the mechanisms involved in the loss of miR-200s in tumoral pancreatic cells. Whereas miR-200 gene promoters appear methylated in mature miR-200 deficient cell lines, miR-200 precursors are detected in nuclear but not cytoplasmic compartment of these cells, indicating that promoter hypermethylation is not sufficient to explain the deficit of mature miR-200s.

Cadherin-1 and cadherin-3 cooperation determines the aggressiveness of pancreatic ductal adenocarcinoma.

Background: Pancreatic ductal adenocarcinoma (PDAC) is characterised by an extensive tissue invasion and an early formation of metastasis. Alterations in the expression of cadherins have been reported in PDAC. Yet, how these changes contribute to tumour progression is poorly understood.

Saccharomyces boulardii CNCM I-745 Restores intestinal Barrier Integrity by Regulation of E-cadherin Recycling.

Background And Aims: Alteration in intestinal permeability is the main factor underlying the pathogenesis of many diseases affecting the gut, such as inflammatory bowel disease [IBD]. Characterization of molecules targeting the restoration of intestinal barrier integrity is therefore vital for the development of alternative therapies. The yeast Saccharomyces boulardii CNCM I-745 [Sb], used to prevent and treat antibiotic-associated infectious and functional diarrhea, may have a beneficial effect in the treatment of IBD.

Interplay between cadherins and α2β1 integrin differentially regulates melanoma cell invasion.

Background: Malignant transformation of melanocytes frequently coincides with an alteration in the expression of cell-cell adhesion molecules (cadherins) and cell-extracellular matrix proteins (integrins). How these two adhesion systems interplay to impact on cell invasion remains to be described in melanoma.

Methods: Cell adhesion networks were localised by immunofluorescence in human primary cutaneous melanoma, metastatic melanoma in the lymph nodes, and melanoma cell lines.

Exosomal lipids induce human pancreatic tumoral MiaPaCa-2 cells resistance through the CXCR4-SDF-1α signaling axis.

We previously reported that exosomes secreted by human pancreatic tumor cells induce cell death through the inhibition of the Notch-1 survival pathway (Ristorcelli et al., 2009). We demonstrated that exosomal lipids evoked apoptosis of human pancreatic cancer SOJ-6 cells.

Saccharomyces boulardii improves intestinal epithelial cell restitution by inhibiting αvβ5 integrin activation state.

Intestinal epithelial cell damage is frequently seen in the mucosal lesions of infectious or inflammatory bowel diseases such as ulcerative colitis or Crohn's disease. Complete remission of these diseases requires both the disappearance of inflammation and the repair of damaged epithelium. Saccharomyces boulardii (Sb, Biocodex) is a non-pathogenic yeast widely used as a preventive and therapeutic probiotic for the prevention and treatment of diarrhea and other gastrointestinal disorders.

αv integrin processing interferes with the cross-talk between αvβ5/β6 and α2β1 integrins.

Background Information: Previous studies have reported that cross-talk between integrins may be an important regulator of integrin-ligand binding and subsequent signalling events that control a variety of cell functions in many tissues. We previously demonstrated that αvβ5/β6 integrin represses α2β1-dependent cell migration. The αv subunits undergo an endoproteolytic cleavage by protein convertases, whose role in tumoral invasion has remained controversial.

Saccharomyces boulardii improves intestinal cell restitution through activation of the α2β1 integrin collagen receptor.

Intestinal epithelial cell damage is frequently seen in the mucosal lesions of inflammatory bowel diseases such as ulcerative colitis or Crohn's disease. Complete remission of these diseases requires both the cessation of inflammation and the migration of enterocytes to repair the damaged epithelium. Lyophilized Saccharomyces boulardii (Sb, Biocodex) is a nonpathogenic yeast widely used as a therapeutic agent for the treatment and prevention of diarrhea and other gastrointestinal disorders.

Lebectin increases N-cadherin-mediated adhesion through PI3K/AKT pathway.

Cell adhesion molecules, including cadherins and integrins, play an essential role during tumor progression and represent potential targets for the development of new therapeutic agents. We previously showed that lebectin, a C-type lectin protein (CLP) issued from Macrovipera lebectina snake venom, inhibits integrin-mediated migration of IGR39 melanoma cells. Here we assessed whether lebectin modulates cell-cell adhesion.

Early adhesion induces interaction of FAK and Fyn in lipid domains and activates raft-dependent Akt signaling in SW480 colon cancer cells.

Integrin-dependent interaction of epithelial tumor cells with extracellular matrix (ECM) is critical for their migration, but also for hematogenous dissemination. Elevated expression and activity of Src family kinases (SFKs) in colon cancer cells is often required in the disease progression. In this work, we highlighted how focal adhesion kinase (FAK) and SFKs interacted and we analyzed how PI3K/Akt and MAPK/Erk1/2 signaling pathways were activated in early stages of colon cancer cell adhesion.

Mature DC from skin and skin-draining LN retain the ability to acquire and efficiently present targeted antigen.

Skin-draining LN contain several phenotypically distinguishable DC populations, which may be immature or mature. Mature DC are generally considered to have lost the capacity to acquire and present newly encountered Ag. Using antibody-opsonized liposomes as Ag carriers, we show that mature DC purified from skin explants are able to efficiently capture liposomes, process Ag encapsulated within them and activate Ag-specific CD4(+) T cells.

CD4 T cell help is required for primary CD8 T cell responses to vesicular antigen delivered to dendritic cells in vivo.

Insight into the mechanisms by which dendritic cells (DC) present exogenous antigen to T cells is of major importance in the design of vaccines. We examined the effectiveness of free antigen as well as antigen with lipopolysaccharide, emulsified in complete Freund's adjuvant, and antigen encapsulated in liposomes in activating adoptively transferred antigen-specific CD4 and CD8 T cells. When contained in liposomes, 100- to 1000-fold lower antigen amounts were as efficient in inducing proliferation and effector functions of CD4 and CD8 T cells in draining lymph nodes as other antigen forms.

Overexpression of cellular prion protein induces an antioxidant environment altering T cell development in the thymus.

Cellular prion protein (PrP(C)) is an ubiquitously expressed glycoprotein whose roles are still widely discussed, particularly in the field of immunology. Using TgA20- and Tg33-transgenic mice overexpressing PrP(C), we investigated the consequences of this overexpression on T cell development. In both models, overexpression of PrP(C) induces strong alterations at different steps of T cell maturation.