Search results for "IMM"
showing 10 items of 18201 documents
Tumor-Derived Prostaglandin E2 Promotes p50 NF-κB-Dependent Differentiation of Monocytic MDSCs
2020
Abstract Myeloid-derived suppressor cells (MDSC) include immature monocytic (M-MDSC) and granulocytic (PMN-MDSC) cells that share the ability to suppress adaptive immunity and to hinder the effectiveness of anticancer treatments. Of note, in response to IFNγ, M-MDSCs release the tumor-promoting and immunosuppressive molecule nitric oxide (NO), whereas macrophages largely express antitumor properties. Investigating these opposing activities, we found that tumor-derived prostaglandin E2 (PGE2) induces nuclear accumulation of p50 NF-κB in M-MDSCs, diverting their response to IFNγ toward NO-mediated immunosuppression and reducing TNFα expression. At the genome level, p50 NF-κB promoted binding …
Melanoma in the liver: Oxidative stress and the mechanisms of metastatic cell survival.
2020
Abstract Metastatic melanoma is a fatal disease with a rapid systemic dissemination. The most frequent target sites are the liver, bone, and brain. Melanoma metastases represent a heterogeneous cell population, which associates with genomic instability and resistance to therapy. Interaction of melanoma cells with the hepatic sinusoidal endothelium initiates a signaling cascade involving cytokines, growth factors, bioactive lipids, and reactive oxygen and nitrogen species produced by the cancer cell, the endothelium, and also by different immune cells. Endothelial cell-derived NO and H2O2 and the action of immune cells cause the death of most melanoma cells that reach the hepatic microvascul…
MiR-205-5p inhibition by locked nucleic acids impairs metastatic potential of breast cancer cells.
2018
AbstractMir-205 plays an important role in epithelial biogenesis and in mammary gland development but its role in cancer still remains controversial depending on the specific cellular context and target genes. We have previously reported that miR-205-5p is upregulated in breast cancer stem cells targeting ERBB pathway and leading to targeted therapy resistance. Here we show that miR-205-5p regulates tumorigenic properties of breast cancer cells, as well as epithelial to mesenchymal transition. Silencing this miRNA in breast cancer results in reduced tumor growth and metastatic spreading in mouse models. Moreover, we show that miR-205-5p knock-down can be obtained with the use of specific lo…
HMG-CoA reductase promotes protein prenylation and therefore is indispensible for T-cell survival.
2017
AbstractStatins are a well-established family of drugs that lower cholesterol levels via the competitive inhibition of the enzyme 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR). In addition, the pleiotropic anti-inflammatory effects of statins on T cells make them attractive as therapeutic drugs in T-cell-driven autoimmune disorders. Since statins do not exclusively target HMGCR and thus might have varying effects on different cell types, we generated a new mouse strain allowing for the tissue-specific deletion of HMGCR. Deletion of HMGCR expression in T cells led to a severe decrease in their numbers with the remaining cells displaying an activated phenotype, with an increased pro…
Growth differentiation factor 15 as a radiation-induced marker in oral carcinoma increasing radiation resistance.
2015
Background Growth differentiation factor 15 (GDF15) is involved in tumor pathogenesis of oral squamous cell carcinoma (OSCC). The aim of this study was an investigation of the potential influence of GDF15 on radioresistance of OSCC cells in vitro. Methods Oral squamous cell carcinoma cell lines were irradiated with 0, 2, or 6 Gy, and GDF15 expression in the supernatant per survived cell colony was examined with ELISA. Non-irradiated and OSCC cell lines irradiated with 6 Gy were evaluated for GDF15 expression using immunofluorescent staining. For further investigation of GDF15 effects on radioresistance, a GDF15 knockdown model in a human OSCC cell line was established, and apoptotic activit…
Tumour mutational burden as a biomarker for immunotherapy: Current data and emerging concepts
2020
International audience; Treatment with immune checkpoint inhibitors targeting programmed cell death protein 1 (PD-1) or its ligand (PD-L1) can generate durable responses in various cancer types, but only in a subset of patients. The use of predictive biomarkers for response to PD-1/PD-L1 inhibitors is critical for patient selection. Expression of PD-L1 has demonstrated utility in patient selection. Tumour mutational burden (TMB) is an emerging biomarker for response to PD-1/PD-L1 inhibitors. The evaluation of this biomarker is based on the hypothesis that a high number of mutations in somatic exonic regions will lead to an increase in neoantigen production, which could then be recognised by…
A Pan-Cancer Approach to Predict Responsiveness to Immune Checkpoint Inhibitors by Machine Learning
2019
Immunotherapy by using immune checkpoint inhibitors (ICI) has dramatically improved the treatment options in various cancers, increasing survival rates for treated patients. Nevertheless, there are heterogeneous response rates to ICI among different cancer types, and even in the context of patients affected by a specific cancer. Thus, it becomes crucial to identify factors that predict the response to immunotherapeutic approaches. A comprehensive investigation of the mutational and immunological aspects of the tumor can be useful to obtain a robust prediction. By performing a pan-cancer analysis on gene expression data from the Cancer Genome Atlas (TCGA, 8055 cases and 29 cancer types), we …
A receptor-antibody hybrid hampering MET-driven metastatic spread
2021
AbstractBackgroundThe receptor encoded by the MET oncogene and its ligand Hepatocyte Growth Factor (HGF) are at the core of the invasive-metastatic behavior. In a number of instances genetic alterations result in ligand-independent onset of malignancy (METaddiction). More frequently, ligand stimulation of wild-type MET contributes to progression toward metastasis (METexpedience). Thus, while MET inhibitors alone are effective in the first case, combination therapy with ligand inhibitors is required in the second condition.MethodsIn this paper, we generated hybrid molecules gathering HGF and MET inhibitory properties. This has been achieved by ‘head-to-tail’ or ‘tail-to-head’ fusion of a sin…
Reduced Breast Tumor Growth after Immunization with a Tumor-Restricted MUC1 Glycopeptide Conjugated to Tetanus Toxoid.
2018
Abstract Preventive vaccination against tumor-associated endogenous antigens is considered to be an attractive strategy for the induction of a curative immune response concomitant with a long-lasting immunologic memory. The mucin MUC1 is a promising tumor antigen, as its tumor-associated form differs from the glycoprotein form expressed on healthy cells. Due to aberrant glycosylation in tumor cells, the specific peptide epitopes in its backbone are accessible and can be bound by antibodies induced by vaccination. Breast cancer patients develop per se only low levels of T cells and antibodies recognizing tumor-associated MUC1, and clinical trials with tumor-associated MUC1 yielded unsatisfac…
9-ING-41, a small-molecule glycogen synthase kinase-3 inhibitor, is active in neuroblastoma.
2018
Advanced stage neuroblastoma is a very aggressive pediatric cancer with limited treatment options and a high mortality rate. Glycogen Synthase Kinase-3β (GSK-3β) is a potential therapeutic target in neuroblastoma. Using immunohistochemical staining, we observed positive GSK-3β expression in 67% of human neuroblastomas (34 out of 51 cases). Chemically distinct GSK-3 inhibitors (AR-A014418, TDZD8 and 9-ING-41), suppressed the growth of neuroblastoma cells whereas 9-ING-41, a clinically relevant small molecule GSK-3β inhibitor with broad spectrum pre-clinical antitumor activity, being the most potent. Inhibition of GSK-3 resulted in a decreased expression of the antiapoptotic molecule XIAP and…