0000000000645935

AUTHOR

Michael Hölzel

showing 2 related works from this author

Melanomas resist T-cell therapy through inflammation-induced reversible dedifferentiation.

2012

Adoptive cell transfer therapies (ACTs) with cytotoxic T cells that target melanocytic antigens can achieve remissions in patients with metastatic melanomas, but tumours frequently relapse. Hypotheses explaining the acquired resistance to ACTs include the selection of antigen-deficient tumour cell variants and the induction of T-cell tolerance. However, the lack of appropriate experimental melanoma models has so far impeded clear insights into the underlying mechanisms. Here we establish an effective ACT protocol in a genetically engineered mouse melanoma model that recapitulates tumour regression, remission and relapse as seen in patients. We report the unexpected observation that melanoma…

Adoptive cell transfermedicine.medical_treatmentCellular differentiationT cellBiologyProinflammatory cytokineMiceAntigenCell Line TumormedicineTumor MicroenvironmentCytotoxic T cellAnimalsHumansMelanomaCell ProliferationInflammationMultidisciplinaryTumor Necrosis Factor-alphaMelanomaCell DifferentiationImmunotherapyCell Dedifferentiationmedicine.diseaseAdoptive TransferMice Inbred C57BLDisease Models Animalmedicine.anatomical_structureImmunologyImmunotherapyNeoplasm TransplantationT-Lymphocytes Cytotoxicgp100 Melanoma AntigenNature
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Spleen tyrosine kinase (SYK) is a potential target for the treatment of cutaneous lupus erythematosus patients

2016

Spleen tyrosine kinase (SYK) is a protein kinase involved in cell proliferation and the regulation of inflammatory pathways. Due to the increasing evidence that kinase inhibitors have potential as specific anti-inflammatory drugs, we have investigated the potential for SYK inhibition as a therapeutic target in autoimmune diseases, particularly cutaneous lupus erythematosus (CLE). Skin samples of patients with different CLE subtypes and appropriate controls were analysed for the expression of SYK and SYK-associated pro-inflammatory mediators via gene expression analysis and immunohistochemistry. The functional role of SYK in keratinocytes was investigated in vitro, using LE-typical pro-infla…

0301 basic medicineCell typeSykchemical and pharmacologic phenomenaDermatologyenvironment and public healthBiochemistry03 medical and health sciencesImmune systemDownregulation and upregulationLupus Erythematosus CutaneousmedicineHumansSyk KinasePhosphorylationMolecular BiologyCells CulturedInnate immune systemSystemic lupus erythematosusKinasebusiness.industryhemic and immune systemsmedicine.diseaseenzymes and coenzymes (carbohydrates)030104 developmental biologyCase-Control StudiesImmunologyCytokinesPhosphorylationbiological phenomena cell phenomena and immunitybusinessExperimental Dermatology
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