0000000000054135

AUTHOR

Marina Kreutz

showing 3 related works from this author

Tumor-derived lactic acid modulates dendritic cell activation and antigen expression.

2005

The tumor milieu can influence dendritic cell (DC) differentiation. We analyzed DC differentiation in a 3-dimensional tumor model and propose a new mechanism of DC modulation by the tumor environment. Monocytes were cultured in the presence of IL-4 and GM-CSF within multicellular tumor spheroids (MCTSs) generated from different tumor cell lines. Monocytes invaded the MCTSs and differentiated into tumor-associated dendritic cells (TADCs). The antigen expression was altered on TADCs independent of the culture conditions (immature/mature DCs, Langerhans cells) and IL-12 secretion was reduced. Supernatants of MCTSs could partially transfer the suppressive effect. Conditioned media from urotheli…

Cellular differentiationImmunologyBiologyBiochemistryMonocyteschemistry.chemical_compoundCell Line TumorNeoplasmsSpheroids CellularmedicineHumansSecretionLactic AcidMelanomaCell DifferentiationCell BiologyHematologyDendritic cellDendritic CellsTumor-Derivedmedicine.diseaseCoculture TechniquesCell biologyLactic acidTumor EscapechemistryCell cultureCytokinesTumor EscapeBlood
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Tumor-Derived Lactic Acid Modulates Dendritic Cell Activation and Differentiation.

2004

Abstract The tumor milieu can influence DC differentiation in vivo and in vitro. We analyzed DC differentiation in a 3-dimensional tumor model and propose a new mechanism of DC modulation by the tumor environment. Monocytes were cultured in the presence of IL-4 and GM-CSF within multicellular tumor spheroids (MCTS) generated from urothelial carcinoma (J82, UMUC3) and melanoma cell lines (MelIm, Mel108). Monocytes invaded the tumor spheroids and differentiated into tumor-associated dendritic cells (TADC) that displayed an altered phenotype compared to DC generated without tumor contact. The expression of CD1a was reduced on TADC whereas CD80, CD86 and CD16 were upregulated. In addition, TADC…

CD86MelanomaImmunologyAntigen presentationCellCell BiologyHematologyDendritic cellCD16Biologymedicine.diseaseBiochemistrymedicine.anatomical_structureBiochemistryCell cultureCancer researchmedicineCD80Blood
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LDHA-Associated Lactic Acid Production Blunts Tumor Immunosurveillance by T and NK Cells

2015

Elevated lactate dehydrogenase A (LDHA) expression is associated with poor outcome in tumor patients. Here we show that LDHA-associated lactic acid accumulation in melanomas inhibits tumor surveillance by T and NK cells. In immunocompetent C57BL/6 mice, tumors with reduced lactic acid production (Ldhalow) developed significantly slower than control tumors and showed increased infiltration with IFN-γ-producing T and NK cells. However, in Rag2-/-γc-/- mice, lacking lymphocytes and NK cells, and in Ifng-/- mice, Ldhalow and control cells formed tumors at similar rates. Pathophysiological concentrations of lactic acid prevented upregulation of nuclear factor of activated T cells (NFAT) in T and…

Male0301 basic medicineCell SurvivalPhysiologyT-LymphocytesT cellApoptosisCell CountCD8-Positive T-LymphocytesBiologySodium LactateInterferon-gamma03 medical and health scienceschemistry.chemical_compoundInterleukin 21Downregulation and upregulationCell Line TumormedicineAnimalsHumansLactic AcidImmunologic SurveillanceMelanomaMolecular BiologyCell ProliferationL-Lactate DehydrogenaseNFATC Transcription FactorsNFATCell Biologymedicine.diseaseUp-RegulationLactic acidIsoenzymesKiller Cells NaturalMice Inbred C57BLPhenotype030104 developmental biologymedicine.anatomical_structurechemistryCell cultureImmunologyCancer researchInterleukin 12CytokinesLactate Dehydrogenase 5GlycolysisInfiltration (medical)Cell Metabolism
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