0000000000158321

AUTHOR

Nicola Bielefeld

showing 3 related works from this author

Acquired IFNγ resistance impairs anti-tumor immunity and gives rise to T-cell-resistant melanoma lesions

2016

Melanoma treatment has been revolutionized by antibody-based immunotherapies. IFNγ secretion by CD8+ T cells is critical for therapy efficacy having anti-proliferative and pro-apoptotic effects on tumour cells. Our study demonstrates a genetic evolution of IFNγ resistance in different melanoma patient models. Chromosomal alterations and subsequent inactivating mutations in genes of the IFNγ signalling cascade, most often JAK1 or JAK2, protect melanoma cells from anti-tumour IFNγ activity. JAK1/2 mutants further evolve into T-cell-resistant HLA class I-negative lesions with genes involved in antigen presentation silenced and no longer inducible by IFNγ. Allelic JAK1/2 losses predisposing to …

Patient-Specific Modeling0301 basic medicineSkin NeoplasmsBiopsyT-LymphocytesDNA Mutational AnalysisDatasets as TopicGeneral Physics and AstronomyAntineoplastic Agents ImmunologicalMutation RatePrecision MedicineMelanomaSkinAntigen PresentationMultidisciplinarybiologyMelanomaQfood and beverages3. Good healthTreatment Outcomemedicine.anatomical_structureImmunotherapyAntibodySignal TransductionScienceT cellAntigen presentationHuman leukocyte antigenArticleGeneral Biochemistry Genetics and Molecular BiologyInterferon-gamma03 medical and health sciencesAntigenAntigens NeoplasmCell Line TumormedicineHumansWhole Genome SequencingHistocompatibility Antigens Class IJanus Kinase 1General ChemistryJanus Kinase 2medicine.disease030104 developmental biologyImmunoeditingDrug Resistance NeoplasmMutationImmunologybiology.proteinTumor EscapeCD8Nature Communications
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Genetic evolution of T-cell resistance in the course of melanoma progression

2014

Abstract Purpose: CD8+ T lymphocytes can kill autologous melanoma cells, but their activity is impaired when poorly immunogenic tumor phenotypes evolve in the course of disease progression. Here, we analyzed three consecutive melanoma lesions obtained within one year of developing stage IV disease for their recognition by autologous T cells. Experimental Design: One skin (Ma-Mel-48a) and two lymph node (Ma-Mel-48b, Ma-Mel-48c) metastases were analyzed for T-cell infiltration. Melanoma cell lines established from the respective lesions were characterized, determining the T-cell–stimulatory capacity, expression of surface molecules involved in T-cell activation, and specific genetic alteratio…

Cancer ResearchB7 Antigensmedicine.medical_treatmentMedizinGene ExpressionT-Lymphocyte Subsetshemic and lymphatic diseasesCluster AnalysisLymphocytesNeoplasm MetastasisLymph nodeMelanomaTumorImmunogenicityMelanomaSingle Nucleotidemedicine.anatomical_structurePhenotypeButorphanolOncologyDisease ProgressionCytokinesEvolutionT cellHuman leukocyte antigenBiologyPolymorphism Single NucleotideArticleCell LineEvolution MolecularLymphocytes Tumor-InfiltratingCell Line TumormedicineHumansGenetic Predisposition to DiseaseTumor-InfiltratingAllelePolymorphismneoplasmsAllelesNeoplasm StagingHistocompatibility Antigens Class IMolecularImmunotherapymedicine.diseaseAlleles; B7 Antigens; Butorphanol; Cell Line Tumor; Cluster Analysis; Cytokines; Disease Progression; Gene Expression; Genetic Predisposition to Disease; Histocompatibility Antigens Class I; Humans; Lymphocytes Tumor-Infiltrating; Melanoma; Mutation; Neoplasm Metastasis; Neoplasm Staging; Phenotype; Polymorphism Single Nucleotide; T-Lymphocyte Subsets; beta 2-Microglobulin; Evolution Molecular; Oncology; Cancer ResearchImmunologyMutationbeta 2-MicroglobulinCD8
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Melanoma Lesions Independently Acquire T-cell Resistance during Metastatic Latency

2016

Abstract Melanoma often recurs after a latency period of several years, presenting a T cell–edited phenotype that reflects a role for CD8+ T cells in maintaining metastatic latency. Here, we report an investigation of a patient with multiple recurrent lesions, where poorly immunogenic melanoma phenotypes were found to evolve in the presence of autologous tumor antigen–specific CD8+ T cells. Melanoma cells from two of three late recurrent metastases, developing within a 6-year latency period, lacked HLA class I expression. CD8+ T cell–resistant, HLA class I–negative tumor cells became clinically apparent 1.5 and 6 years into stage IV disease. Genome profiling by SNP arrays revealed that HLA …

0301 basic medicineCancer ResearchT cellmedicine.medical_treatmentMedizinHuman leukocyte antigenCD8-Positive T-LymphocytesBiology03 medical and health sciencesAntigens NeoplasmmedicineHumansNeoplasm MetastasisMelanomaMelanomaCancerImmunosuppressionmedicine.diseasePhenotypeNeoplasm Proteins030104 developmental biologymedicine.anatomical_structureOncologyLatency stageImmunologyCD8Cancer Research
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