Inflammatory macrophages and dendritic cells guiding cancer manifestation
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1 Inflammatory macrophages and dendritic cells guiding cancer manifestation E. Marion Schneider 1, David Zielberg 2, Haouraa Mostafa 1, Karl Aigner 3, Andrej Pala 4, Michael Georgieff 5, C Rainer Wirtz 4, Knut M Wittkowski 6 ICoMI May 2017
2 Tumor cells and MDSCs
3 Which mechanisms drive this process? and how to combat?
4 Inflammatory stimuli sterile pathogen Inflammatory cells Mφ, dendritic cells Signaling Receptors and transcription factors polymorphisms Biomarkers and inflammatory diseases Malignancies, sepsis
5 trigger inflammatory macrophages and dendritic cells and pave the way to cancer manifestation ICoMI May 2017
6 Inflammation Inflammation/Stress - Infection - Tumors - Aging acute chronic inflammation base line Fei Chen and Vince Catranova Cancer Research 2007; 67:(23), Dec, 2007
7 P2X7 The inflammasome - basic principle of inflammation and infection NLR ASC Pro IL-1b TNF-a IL-1b IL-1b
8 Traumatic stimulus trauma DNA cell damage and lysis ATP inflammation mature-il-1β pinocytosis P2X7 receptor TLR9 endosomal membrane plasma membrane K + efflux Ca ++ influx mature-il-1β NF-κB pro-il-1β inflammasome activated inflammasome
9 PAMP DAMP PAMP DAMP PAMP DAMP ATP MyD88 / IRE NF B Inflammasome Kawai T, Akira S: TLR Signaling. Cell Death and Differentiation 13, (2006) TNF-α IL-1β
10 Mikroparticle ATP Vacuole formation /autophagosome
11 3h ATP Schneider et al. 2011
12 M1 12
13 13094His Morphology Phalloidin-TexasRed 13
14 macropinocytosis Mikroparticle release Actin cytoskeleton 14
15
16 idc mdc 2 2 current amplitude (na) CsA current amplitude (na) CsA time (s) time (s) cultured DC wt cultured DC 1513 mut CsA CsA
17 Genetic differences
18 Individuality of the cytokine response in vivo: IL-1β IL-1β pg/ml
19 Individuality of the cytokine response in vivo: Ferritin 1000,00 900,00 Plasma Ferritin (ng/ml) 800,00 700,00 600,00 500,00 400,00 300,00 200,00 100,00 0,
20 Metabolic differences in M1 vs. M2 macrophages NOS Ferritin Glutathion Glycolysis Cox2 IL-1β Orchestration of Metabolism by Macrophages Subhra K. Biswas and Alberto Mantovani CD163 Arginase 1 OXPHOS Cox1 Fatty acid oxidation Folate receptor
21 Signaling
22 Genetic polymorphisms and autoimmune diseases IRF-5 SNPs linked to MS, RA, SLE IRF-5 is essential for the induction of a range of pro-inflammatory genes, including IL-6, IL-12, and TNF, but not IFN-α, and is found in a trimeric complex with MyD88 and TRAF6.
23 IRF5 (rs ) SNP distribution control IRF5-Haplotypen (Ref. data) wt mutiert patients IRF5-Genotypes homozygous mut mut allele wt allele homozygous wt heterozygous
24 Cytoskeleton, Motility and Pathogen Uptake veils filopodia
25 Cytoskeleton, Motility and Virus Infection control HIV infected
26 Inflammatory macrophages differ in microparticle release
27 Biomarkers tested in patients undergoing regional chemotherapy Schneider et al. DZO, 2017
28 Biomarkers tested in patients undergoing regional chemotherapy Schneider et al. DZO, 2017
29 Biomarkers tested in patients undergoing regional chemotherapy Schneider et al. DZO, 2017
30 Leukocyte counts are relevant for a beneficial outcome in patients undergoing regional chemotherapy Schneider et al. DZO, 2017
31 Granulocyte MDSC in tumor tissue J (CD15 stain)
32 IL-7, SDF-1 play a major role in patients with a beneficial outcome after regional chemotherapy Schneider et al. DZO, 2017
33 Lymphoid precursors, CD2 expression densities and mature dendritic cells are relevant Schneider et al. DZO, 2017
34 Biomarkers in glioblastoma CD39+ Treg Crosstalk Mostafa et al. J Hem Oncol. 2016
35 Morphology sepsis GBM MAS Blood donor 35
36 Surveillance of inflammation by NK cells
37 Surveillance of inflammation by NK cells
38 Mostafa et al. 2016
39 Biomarkers in glioblastoma Mostafa et al. J Hem Oncol. 2016
40 David Zielberg Karl Aigner Harald Hohmann Weidong Du Knut Wittkowski Haouraa Mostafa Philip Sander Harald Hohmann Karl Föhr Sarah Flacke Peter Steffen Peter Bäuerle Silvia Schmid Karl Bechter (BKK Günzburg) Horst G. Maxeiner Manfred Schmolz (HotScreen) Nicole Schneiderhan-Marra Thomas O. Joos
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