A5084114891- Immunotherapy and Immune Responses
- CAR-T cell therapy research
- Cancer Immunotherapy and Biomarkers
- Immune Cell Function and Interaction
- vaccines and immunoinformatics approaches
- T-cell and B-cell Immunology
- Lung Cancer Treatments and Mutations
- Bioinformatics and Genomic Networks
- Monoclonal and Polyclonal Antibodies Research
- Endometrial and Cervical Cancer Treatments
- SARS-CoV-2 and COVID-19 Research
- Computational Drug Discovery Methods
- Hematopoietic Stem Cell Transplantation
- Lymphoma Diagnosis and Treatment
- Single-cell and spatial transcriptomics
- Advanced Biosensing Techniques and Applications
- Genomics and Chromatin Dynamics
- Receptor Mechanisms and Signaling
- Gene expression and cancer classification
- Acute Myeloid Leukemia Research
- HER2/EGFR in Cancer Research
- Calcium signaling and nucleotide metabolism
- Cancer Genomics and Diagnostics
- Genomics and Phylogenetic Studies
- Galectins and Cancer Biology
Oslo Cancer Cluster
2019-2024
Cancer Registry of Norway
2022-2024
Oslo University Hospital
2010-2019
University of Oslo
2010-2019
Norwegian Cancer Society
2010-2017
Institute of Electrical and Electronics Engineers
2016
Regional Municipality of Niagara
2016
IEEE Computer Society
2016
University of Bergen
2013
Norwegian Computing Center
2011-2013
The functional diversity of natural killer (NK) cell repertoires stems from differentiation, homeostatic, receptor-ligand interactions and adaptive-like responses to viral infections. In the present study, we generated a single-cell transcriptional reference map healthy human blood- tissue-derived NK cells, with temporal resolution fate-specific expression gene-regulatory networks defining differentiation. Transfer learning facilitated incorporation tumor-infiltrating transcriptomes (39...
Maintenance of genome integrity is critical importance to cells. To identify key regulators genomic integrity, we screened a human cell line with kinome small interfering RNA library. WEE1, major regulator mitotic entry, and CHK1 were among the genes identified. Both kinases are important negative CDK1 -2. Strikingly, WEE1 depletion rapidly induced DNA damage in S phase newly replicated DNA, which was accompanied by marked increase single-stranded DNA. This dependent on -2 as well...
Purpose: To evaluate the safety, efficacy, and immunobiological correlates of allogeneic NK-cell-based therapy in primary chemotherapy-refractory or relapsed high-risk myelodysplastic syndrome (MDS), secondary AML (MDS/AML), de novo patients.Experimental Design: Sixteen patients received fludarabine/cyclophosphamide conditioning combined with total lymphoid irradiation followed by adoptive immunotherapy IL2-activated haploidentical NK cells.Results: NK-cell infusions were well-tolerated,...
Abstract Inhibitory signaling during natural killer (NK) cell education translates into increased responsiveness to activation; however, the intracellular mechanism for functional tuning by inhibitory receptors remains unclear. Secretory lysosomes are part of acidic lysosomal compartment that mediates signalling in several types. Here we show educated NK cells expressing self-MHC specific immunoglobulin-like (KIR) accumulate granzyme B dense-core secretory converge close centrosome. This...
Abstract The global population is at present suffering from a pandemic of Coronavirus disease 2019 (COVID-19), caused by the novel coronavirus Severe Acute Respiratory Syndrome 2 (SARS-CoV-2). goal this study was to use artificial intelligence (AI) predict blueprints for designing universal vaccines against SARS-CoV-2, that contain sufficiently broad repertoire T-cell epitopes capable providing coverage and protection across population. To help achieve these aims, we profiled entire...
The immense increase in the generation of genomic scale data poses an unmet analytical challenge, due to a lack established methodology with required flexibility and power. We propose first principled approach statistical analysis sequence-level information. provide growing collection generic biological investigations that query pairwise relations between tracks, represented as mathematical objects, along genome. Genomic HyperBrowser implements is available at http://hyperbrowser.uio.no .
Cancer vaccines represent a novel treatment modality with complementary mode of action addressing crucial bottleneck for checkpoint inhibitor (CPI) efficacy. CPIs are expected to release brakes in T-cell responses elicited by vaccination, leading more robust immune responses. Increased antitumor may confer increased activity patients less immunogenic tumors, subgroup achieve reduced benefit from alone. In this trial, telomerase-based vaccine was combined pembrolizumab assess the safety and...
LTX-315 is an oncolytic peptide that elicits both local and systemic immune responses upon intratumoral injection. In the present pilot trial, we treated patients with metastatic soft tissue sarcoma combination of adoptive T-cell therapy using in vitro expanded tumor-infiltrating lymphocytes. Six heavily pretreated were included trial which four proceeded to therapy. Overall, treatment was considered safe only expected manageable toxicity. The best overall clinical response stable disease...
The accurate screening of tumor genomic landscapes for somatic mutations using high-throughput sequencing involves a crucial step in precise clinical diagnosis and targeted therapy. However, the complex inherent features cancer tissue, especially, genetic intra-heterogeneity coupled with problem alignment artifacts, makes variant calling challenging task. Current filtering strategies, such as rule-based consensus voting different algorithms, have previously helped to increase specificity,...
Colorectal cancer (CRC) incidence increases with age, and early onset of the disease is an indication genetic predisposition, estimated to cause up 30% all cases. To identify genes associated early-onset CRC, we investigated gene expression levels within a series young patients CRCs who are not known carry any hereditary syndromes (n=24; mean 43 years at diagnosis), compared this from diagnosed older age (n=17; 79 years). Two individual were found be differentially expressed between two...
Natural killer (NK) cell repertoires are made up of phenotypically distinct subsets with different functional properties. The molecular programs involved in maintaining NK repertoire diversity under homeostatic conditions remain elusive. Here, we show that subset-specific proliferation kinetics correlate mTOR activation, and global is maintained through a high degree intra-lineage subset plasticity during interleukin (IL)-15-driven vitro. Slowly cycling sorted KIR+CD56dim cells an induced...
CD8+tumor infiltrating lymphocytes (TILs) are often observed in non-small cell lung cancers (NSCLC). However, the characteristics of CD8+ TILs, especially T-cell populations specific for tumor antigens, remain poorly understood. High throughput single-cell RNA sequencing and receptor (TCR) were performed on TILs from three surgically-resected cancer specimens. Dimensional reduction clustering was using Uniform Manifold Approximation Projection. TIL TCR cancer/testis antigen KK-LC-1 predicted...
The pathogenetic role, including its target genes, of the recurrent 3p12-p14 loss in cervical cancer has remained unclear. To determine onset event during carcinogenesis, we used microarray techniques and found that was most frequent 3p event, occurring 61% 92 invasive carcinomas, only 2% 43 high-grade intraepithelial lesions (CIN2/3), 33% 6 CIN3 adjacent to suggesting a role acquisition invasiveness or early phase. We performed an integrative DNA copy number expression analysis 77 where all...
The brain offers a unique microenvironment that plays an important role in the establishment and progression of metastasis. However, molecular determinants promote development melanoma metastases are largely unknown. Utilizing two species immune-compromised animals, with vivo cultivated metastatic tissues along their corresponding host metastasis model, we here identify events associated metastases. We find transcriptional changes cells, as induced by brain-microenvironment both species,...
The immense increase in availability of genomic scale datasets, such as those provided by the ENCODE and Roadmap Epigenomics projects, presents unprecedented opportunities for individual researchers to pose novel falsifiable biological questions. With this opportunity, however, are faced with challenge how best analyze interpret their genome-scale datasets. A powerful way representing data is feature-specific coordinates relative reference genome assemblies, i.e. tracks. Genomic HyperBrowser...
Abstract Acute and latent human CMV cause profound changes in the NK cell repertoire, with expansion differentiation of educated cells expressing self-specific inhibitory killer Ig-like receptors. In this study, we addressed whether such CMV-induced imprints on donor repertoire influenced outcome allogeneic stem transplantation. Hierarchical clustering high-resolution immunophenotyping data covering key parameters, including frequencies CD56bright, NKG2A+, NKG2C+, CD57+ subsets, as well size...
Abstract Background This clinical trial evaluated a novel telomerase-targeting therapeutic cancer vaccine, UV1, in combination with ipilimumab, patients metastatic melanoma. Translational research was conducted on patient-derived blood and tissue samples the goal of elucidating effects treatment T cell receptor repertoire tumor microenvironment. Methods The an open-label, single-center phase I/IIa study. Eligible had unresectable Patients received up to 9 UV1 vaccinations four ipilimumab...
Abstract The functional diversity of natural killer (NK) cell repertoires stems from differentiation, homeostatic receptor-ligand interactions, and adaptive-like responses to viral infections. Here, we generated a single-cell transcriptional reference map healthy human blood tissue-derived NK cells, with temporal resolution fate-specific expression gene regulator networks defining differentiation. Using transfer learning, transcriptomes tumor-infiltrating cells seven solid tumor types (427...
The HLA complex is the most polymorphic region of human genome, and its improved characterization can help us understand genetics disease as well interplay between cancer immune system. main function genes to recognize "non-self" antigens present them on cell surface T cells, which instigate an response toward infected or transformed cells. While sequence variation in antigen-binding groove may modulate repertoire immunogenic presented alterations expression significantly influence pathogens...
Precise HLA genotyping is of great clinical importance, albeit a challenging bioinformatics endeavor because the hyper polymorphism region. The ever‐increasing availability next‐generation sequencing (NGS) solutions has spurred development several computational methods for predicting genotypes from NGS data. Although some these tools genotype Class I alleles reasonably well, there need to incorporate integrative parameters related ethnicity frequency information, in order improve performance...
MHC Class I protein plays an important role in immunotherapy by presenting immunogenic peptides to anti-tumor immune cells. The repertoires of for various proteins are distinct, which can be reflected their diverse binding motifs. To characterize motifs proteins, vitro experiments have been conducted screen with high affinities hundreds given proteins. However, considering tens thousands known conducting extensive is infeasible, and thus a more efficient scalable way needed.
Differentiation of monocytes into dendritic cells (DCs) is characterised by marked changes in gene expression. The role microRNAs (miRNAs), a new class small endogenous non-coding regulatory RNAs, this process still unclear. We identified miR-223, miR-16, miR-191, miR-24, let-7b, and miR-21 as differentially expressed between monocyte derived DCs. evaluated the expression levels computationally predicted target genes human following stimulation with GM-CSF IL-4. Moreover, transfection...
Histone deacetylase inhibitors (HDACis) like vorinostat are promising radiosensitisers in prostate cancer, but their effect under hypoxia is not known. We investigated gene expression associated with radiosensitisation of normoxic and hypoxic cancer cells by vorinostat.Cells were exposed to normoxia or subjected profiling before irradiation clonogenic survival analysis.Pretreatment led the intrinsically radioresistant DU 145 cells, radiosensitive PC-3 22Rv1 was independent status. Knockdown...