A5082769169- Multiple Myeloma Research and Treatments
- Immunotherapy and Immune Responses
- Ubiquitin and proteasome pathways
- Malaria Research and Control
- Protein Tyrosine Phosphatases
- Protein Degradation and Inhibitors
- Immune Cell Function and Interaction
- Cytokine Signaling Pathways and Interactions
- PI3K/AKT/mTOR signaling in cancer
- vaccines and immunoinformatics approaches
- Protein Kinase Regulation and GTPase Signaling
- Adenosine and Purinergic Signaling
- Peptidase Inhibition and Analysis
- T-cell and B-cell Immunology
- Chemokine receptors and signaling
- Biochemical and Molecular Research
- CAR-T cell therapy research
- Immune Response and Inflammation
- Heat shock proteins research
- Synthesis and Biological Evaluation
- Melanoma and MAPK Pathways
- Complement system in diseases
- TGF-β signaling in diseases
- Cancer Immunotherapy and Biomarkers
- Mosquito-borne diseases and control
Norwegian University of Science and Technology
2015-2024
NTNU Samfunnsforskning
2019
Kyoto University
2019
University of Colorado Anschutz Medical Campus
2019
Mount Sinai Health System
2019
MRC London Institute of Medical Sciences
2011-2012
Medical Research Council
1994-2009
The Francis Crick Institute
2006
Zero to Three
2005
Max Planck Institute for Infection Biology
2001-2005
The capacity of splenic CD11c+ dendritic cell (DC) populations to present antigen (Ag) T cells differs during malarial infection with Plasmodium chabaudi in mice. Both CD11c+CD8+ and CD8− DCs presented peptides on their surface infection. However, although both DC subsets expressing malaria could induce interferon-γ production by CD4 cells, only isolated at the acute phase stimulated Ag-specific proliferation interleukin (IL)-4 -10 from MSP1-specific receptor for Ag transgenic coincidental...
PD1/PDL1-directed therapies have been unsuccessful for multiple myeloma (MM), an incurable cancer of plasma cells in the bone marrow (BM). Therefore, other immune checkpoints such as extracellular adenosine and its immunosuppressive receptor should be considered. CD39 CD73 convert ATP to adenosine, which inhibits T-cell effector functions via A2A (A2AR). We set out investigate whether blocking pathway could a therapy MM.Expression on BM from patients proliferation were determined by flow...
Abstract We investigated genomic and transcriptomic changes in paired tumor samples of 29 in-house multiple myeloma (MM) patients 28 from the MMRF CoMMpass study before after treatment. A change clonal composition was found 46/57 (82%) patients, single-nucleotide variants (SNVs) increased median 67 to 86. The highest increase prevalence genetic aberrations RAS genes (60% 72%), amp1q21 (18% 35%), TP53 (9% 18%). SBS-MM1 mutation signature detected both receiving high low dose melphalan. total...
In this study we set out to investigate whether anti PDL1 or PD–1 treatment targeting the immune system could be used against multiple myeloma. DCs are important in regulating T cell responses tumors. We therefore determined and PDL2 expression on DC populations bone marrow of patients with plasma disorders using multicolour Flow Cytometry. specifically looked at CD141+ CD141- myeloid CD303+ plasmacytoid DC. The majority cells (PC) subpopulations expressed PDL1, but proportion positive PDL1+...
Multiple myeloma (MM) is a hematologic cancer characterized by expansion of malignant plasma cells in the bone marrow. Most patients develop an osteolytic disease, largely caused increased osteoclastogenesis. The marrow hypoxic, and hypoxia may contribute to MM disease progression, including loss. Here we identified interleukin-32 (IL-32) as novel inflammatory cytokine expressed subset primary cell lines. We found that high IL-32 gene expression correlated with inferior survival was higher...
The host response following malaria infection depends on a fine balance between levels of pro-inflammatory and anti-inflammatory mediators resulting in the resolution or immune-mediated pathology. Whilst other components innate immune system contribute to milieu, T cells play major role. For blood-stage malaria, CD4+ γδ are producers IFN-γ that controls parasitaemia, however, role for TH17 secreting IL-17A cytokines, including IL-17F IL-22 has not yet been investigated malaria. have shown...
Splenic microarchitecture is substantially altered during acute malaria infections, which may affect the development and regulation of immune responses. Here we investigated whether engagement host Toll-like receptor 2 (TLR2), TLR4, TLR9, adaptor protein MyD88 required for induction changes antibody responses are modified when immunization takes place period splenic disruption. The alterations in were maximal shortly after peak parasitemia not dependent on TLR2, or they only minimally...
Abstract Obesity is associated with an increased risk of developing multiple myeloma (MM). The molecular mechanisms causing this association complex and incompletely understood. Whether obesity affects bone marrow immune cell composition in not characterized. Here, we examined the effect diet-induced on tumor growth a Vk*MYC (Vk12653) transplant model myeloma. We find that promoted spleen reduced relative number T B cells marrow. Our results suggest may reduce MM surveillance thus contribute to MM.
This work demonstrates that gp96 preparations isolated from cells infected with intracellular bacteria induce cytotoxic T-lymphocyte responses and confer protection. Our findings extend previous reports on the immunogenicity of gp96-associated peptides to antigens derived bacteria. Immunization may therefore represent a promising vaccination strategy against bacterial pathogens.
Lung cancer is the leading cause of death in both sexes worldwide and has a predicted 5-year survival rate <20%. Immunotherapy targeting immune checkpoints such as programmed 1 (PD-1) signaling pathway led to shift paradigm treatment advanced non–small-cell lung (NSCLC) but remains without effect ∼80% patients. Accumulating evidence suggests that several immunosuppressive mechanisms may work together NSCLC. The contribution cooperation between different NSCLC remain unknown. Recently,...
Cancer cells often depend on microenvironment signals from molecules such as cytokines for proliferation and metabolic adaptations. PRL-3, a cytokine-induced oncogenic phosphatase, is highly expressed in multiple myeloma associated with poor outcome this cancer. We studied whether PRL-3 influences metabolism. Cells transduced to express had higher aerobic glycolytic rate, oxidative phosphorylation, ATP production than the control cells. promoted glucose uptake lactate excretion, enhanced...
Multiple myeloma is an incurable cancer with expansion of malignant plasma cells in the bone marrow. Previous studies have shown that monocytes and macrophages marrow milieu are important for tumor growth may play a role drug response. We therefore characterized aspirates by flow cytometry. found there was significant correlation between proportion CX3CR1 (+), CD16(+)CD14(dim) non classical monocytes, percent (PC) patients. The could be stimulated TLR ligands to produce cytokines which...
Characterization of CD8+ T cells in the tumor microenvironment (TME) is important to predict responses checkpoint therapy. The TME multiple myeloma bone marrow, which also an immune organ where are generated and memory stored. presence with other specificities than marrow may affect search for biomarkers immunotherapy myeloma. Here, we found similar proportions PD1+ levels PD1 expression on patients healthy controls. did not correlate load suggesting that at least some were specific...
Phosphatase of regenerating liver-3 (PTP4A3/PRL-3) is a dual-specificity phosphatase that upregulated in various types cancers and related to poor prognosis aggressive tumor behavior. The expression level PRL-3 elevated response several antiapoptotic cytokines, including IL6, cancer cells from patients with multiple myeloma (MM) can promote survival migration. Here, it demonstrated activates Src kinase the IL6-dependent MM cell line INA-6. Inhibition by small-molecule inhibitor or shRNA...
Abstract Background Multiple myeloma (MM) is a hematological malignancy characterized by the clonal expansion of plasma cells in bone marrow. To date, this disease still incurable and novel therapeutic approaches are required. Phosphoglycerate dehydrogenase (PHGDH) first rate-limiting enzyme de novo serine synthesis pathway, it has been attributed to bortezomib-resistance MM. Methods Two different PHGDH inhibitors, CBR5884 NCT-503, were tested against human cell lines, primary MM from...
Interleukin-32 (IL-32) is a nonclassical cytokine expressed in cancers, inflammatory diseases, and infections. Its expression regulated by two different oxygen sensing systems; HIF1α cysteamine dioxygenase (ADO), indicating that IL-32 may be involved the response to hypoxia. We here demonstrate endogenously expressed, intracellular interacts with components of mitochondrial respiratory chain promotes oxidative phosphorylation. Knocking out three myeloma cell lines reduced survival...
Multiple myeloma is an incurable complex disease characterized by clonal proliferation of malignant plasma cells in a hypoxic bone marrow environment. Hypoxia-dependent erythropoietin (EPO)-receptor (EPOR) signaling central various cancers, but the relevance EPOR multiple has not yet been thoroughly investigated. Myeloma cell lines and isolated from patients were used this study. Transcript levels analysed quantitative PCR surface primary flow cytometry. Knockdown short interfering RNA was...
The fast-moving field of dendritic cell (DC) biology is hard to keep pace with. Here we report on advances from the recent Keystone Symposium, “Dendritic Cells at Center Innate and Adaptive Immunity,” organized in Vancouver, BC Feb. 1–7, 2005 by Anne O'Garra, Jacques Banchereau, Alan Sher. New insights into molecular mechanisms DC function their influence immune regulation, role infectious autoimmune disease, new clinical applications are highlighted.
Mesenchymal stem cells, also called mesenchymal stromal MSCs, have great potential in cell therapy partly due to their immunosuppressive properties. How these cells respond chronic inflammatory stimuli is therefore of importance. Toll-like receptors (TLR)s are innate immune that mediate signals response infection, stress, and damage. Caspase-8 involved activation NF-kB downstream TLRs cells. Here we investigated the role caspase-8 regulating TLR-induced cytokine production from human bone...
Multiple myeloma (MM) is an incurable hematologic malignancy resulting from the clonal expansion of plasma cells. MM cells are interacting with components bone marrow microenvironment such as cytokines to survive and proliferate. Phosphatase regenerating liver (PRL)‐3, a cytokine‐induced oncogenic phosphatase, highly expressed in patients mediator metabolic reprogramming cancer To find novel pathways genes regulated by PRL‐3, we characterized global transcriptional response PRL‐3...
Splenic dendritic cells are crucial for controlling the immune response to malaria by initiating a CD4 gamma interferon (IFN-γ) early in blood-stage infection, which contributes parasite clearance as well acute-stage immunopathology. CD8(-) CD11c(high) have been described previously be important antigen-presenting induction of these T cell responses spleens Plasmodium chabaudi-infected mice. However, when isolated during period maximum parasitemia and shortly thereafter, transiently lose...