Tumor-associated macrophages (TAM) represent an abundant cell population of the immune infiltrate in solid tumors and have been shown to orchestrate escape from immune surveillance. Macrophages display a very plastic phenotype which is recapitulated in vitro by classifying certain subsets according to exposure with defined, individual cytokines. The tumor-promoting M2 macrophages are polarized in vitro by differentiating human monocyte-derived macrophages with the T helper cell type 2 (Th2) response cytokines interleukin-4 and interleukin-13 or the immunosuppressive cytokine interleukin-10. Notably, only the latter macrophage subset undergoes apoptosis when treated with the colony stimulating factor 1 receptor (CSF1R) blocking antibody emactuzumab. However, under physiologic conditions the phenotype of TAM is shaped by a combination of cytokines. Hence, we evaluated if the addition of IL-10 to IL-4 or IL-13 differentiated macrophages is able to override IL-4/-13 mediated signaling and to restore susceptibility to emactuzumab. Though addition of IL-10 did not restore emactuzumab susceptibility, we surprisingly detected that only IL-4 differentiated macrophages sustained their specific marker expression while IL-10 skewed the IL-13 differentiated macrophage profile towards the IL-10 regulated phenotype. In-depth characterization by gene expression profiling revealed unique signatures of IL-4+IL-10 and IL-13+IL-10 differentiated macrophage subsets characterized by upregulation of the canonical NFB signaling or Wnt/-catenin signaling pathways, respectively. In silico-based analysis of a large cohort of cancer patients revealed distinct interleukin-4 or interleukin-13 overexpression patterns in a subset of patients with partial co-expression of IL-10 but almost absent IL-4/IL-13 co-expression. These patients may have less TAM depletion under therapy with CSF1R inhibitors.
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Specimen part
View SamplesGene expression profiles from 280 formalin-fixed and paraffin embedded normal and tumor samples of four cancer types
Regulatory T-cell Genes Drive Altered Immune Microenvironment in Adult Solid Cancers and Allow for Immune Contextual Patient Subtyping.
Sex, Age, Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Identifying and avoiding off-target effects of RNase H-dependent antisense oligonucleotides in mice.
Sex, Specimen part, Treatment
View SamplesWe used microarrays to globally profile the gene expression changes observed in liver after 3 days when dosing antisense oligonucleotides in mice
Identifying and avoiding off-target effects of RNase H-dependent antisense oligonucleotides in mice.
Sex, Specimen part, Treatment
View SamplesWe used microarrays to globally profile the gene expression changes observed after 24h when transfecting antisense oligonucleotides in HuH77 cells
Managing the sequence-specificity of antisense oligonucleotides in drug discovery.
Treatment
View SamplesWe used microarrays to globally profile the gene expression changes observed in liver after 3 days when dosing an antisense oligonucleotide in mice
Identifying and avoiding off-target effects of RNase H-dependent antisense oligonucleotides in mice.
Sex, Specimen part, Treatment
View SamplesAn international standardization program towards the application of gene expression profiling in routine leukaemia diagnostics: The MILE study pre-phase.
An international standardization programme towards the application of gene expression profiling in routine leukaemia diagnostics: the Microarray Innovations in LEukemia study prephase.
No sample metadata fields
View SamplesA new method for amplification and labeling of RNA is assessed that permits gene expression microarray analysis of formalin-fixed paraffin embedded tissue (i.e. FFPET) samples.
A novel method of amplification of FFPET-derived RNA enables accurate disease classification with microarrays.
Specimen part, Treatment
View SamplesThese data can be used for evaluation of the clinical utility of the research-based PAM50 subtype predictor in predicting pathological complete response (pCR) and event-free survival (EFS) in women enrolled in the NeOAdjuvant Herceptin (NOAH) trial.
Research-based PAM50 subtype predictor identifies higher responses and improved survival outcomes in HER2-positive breast cancer in the NOAH study.
Age, Treatment, Race
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Preclinical biomarkers for a cyclin-dependent kinase inhibitor translate to candidate pharmacodynamic biomarkers in phase I patients.
Specimen part, Cell line
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