Project description:Effective targeting of cancer-associated fibroblasts (CAFs) is hindered by the lack of specific biomarkers and a poor understanding of the mechanisms by which different populations of CAFs contribute to cancer progression. While the role of TGFβ in CAFs is well-studied, less attention has been focused on a structurally and functionally similar protein, Activin A (encoded by INHBA), which is typically associated with poor survival and advanced stage in ovarian cancer. Here, we identified INHBA(+) CAFs as key players in tumor promotion and immune evasion. In syngeneic ovarian cancer mouse models, intraperitoneal injection of the Activin A neutralizing antibody attenuated tumor progression and infiltration with the host INHBA(+) CAFs and M2 macrophages. Collectively, our study identified an INHBA(+) subset of pro-tumoral CAFs as a potential therapeutic target in ovarian cancer.
Project description:Saliva based diagnostics is a rapidly evolving field due to the large potential of saliva and the simple sample collection. A systematic comparison of IgG antibody profiles in saliva and plasma is currently lacking in scientific literature. Our hypothesis is that IgG profiles are equal in blood and saliva. By showing the equality of the profiles and relative IgG antigenic reactivities towards proteins and peptides we provide evidence that plasma IgG reactivities can be inferred from saliva IgG reactivities. IgG antibodies were isolated from human saliva and plasma samples. The reactivities of IgG isolates were analysed on peptide microarrays displaying linear epitopes of EBV (EBNA1 protein) and HBV (Large envelope protein) virus. Peptide arrays were printed by JPT Peptide Technologies (Berlin, Germany). We show high similarity of saliva and plasma IgG profiles on these two platforms and argue for generalisation from this subset to the whole immunological IgG antibody profile.
Project description:Saliva based diagnostics is a rapidly evolving field due to the large potential of saliva and the simple sample collection. A systematic comparison of IgG antibody profiles in saliva and plasma is currently lacking in scientific literature. Our hypothesis is that IgG profiles are equal in blood and saliva. By showing the equality of the profiles and relative IgG antigenic reactivities towards proteins and peptides we provide evidence that plasma IgG reactivities can be inferred from saliva IgG reactivities. IgG antibodies were isolated from human saliva and plasma samples. The reactivities of IgG isolates were analysed on peptide microarrays displaying linear epitopes of EBV (EBNA1 protein) and HBV (Large envelope protein) virus. Peptide arrays were printed by JPT Peptide Technologies (Berlin, Germany). We show high similarity of saliva and plasma IgG profiles on these two platforms and argue for generalisation from this subset to the whole immunological IgG antibody profile.
Project description:Whole genome ChIP-chip study using human liver cell line HepG2 and anti-Histone H3 acetyl K9/14 (06-599); USF1 antibody (H-86, sc-8983); USF2 antibody (C-20, sc-862) and normal rabbit IgG (12-370). Three completely independent biological replicates were performed for each antibody, obtaining the corresponding input as total genomic DNA reference. Hybridizations were performed using Affymetrix GeneChip Human Tiling 2.0R Array set (7 arrays set).
Project description:Genetically engineered organoids with the genetic background VBPNA were injected subcutaneously into immunocompetent mice. The mice were treated with CD4 T cells depletion antibody, CD8 T cell depletion antibody or IgG control. The tumors sizes were measured weekly. The intent of the experiment was to determine if the distinct T cell population have an effect on tumor growth, cancer cell state and immune cells.
Project description:The interaction of natural killer (NK) cells with dendritic cells (DC) results in reciprocal cell activation through the interaction of membrane proteins and the release of soluble factors. Here we report that in NK-DC cocultures, among a set of 84 cytokines investigated, activin A was the second highest induced gene, with CXCL8 being the most upregulated one. Activin A is a member of the TGF-β superfamily and was previously shown to possess both pro- and antiinflammatory activities. In NK-DC cocultures, the induction of activin A required cell contact and was dependent on the presence of proinflammatory cytokines (i.e. IFN-γ, TNF-α and GM-CSF) as well as on NK cell-mediated DC killing. CD1+ DC were the main activin A producer cells among myeloid blood DC subsets. In NK-DC cocultures, inhibition of acitivn A by follistatin, a natural inhibitory protein, or by a specific blocking antibody, resulted in the upregulation of proinflammatory cytokine release (i.e. IL-6, IL-8, TNF-α) by DC and in the increase of DC maturation. In conclusion, our study reports that activin A, produced during NK-DC interactions, represents a relevant negative feedback mechanism that might function to prevent excessive immune activation by DC.