Journal: Cell Reports Medicine

Article Title: GATA6 identifies an immune-enriched phenotype linked to favorable outcomes in patients with pancreatic cancer undergoing upfront surgery

doi: 10.1016/j.xcrm.2024.101557

Figure Lengend Snippet: Schematic overview of the methodological steps Schematic overview of the study methodology. Each square represents a methodological step: (1) patient inclusion and clinical procedure, (2) GATA6 IHC staining and tertile grouping, (3) Cox proportional hazards regression modeling, (4) Spearman correlation analysis between GATA6 IHC and classical/basal-like markers, (5) transcriptomic immune profiling using NanoString, and (6) digital spatial protein immune profiling using GeoMx. The digital spatial profiler (DSP) square includes microscopical images of treatment-naive sections illustrating immunofluorescent staining for ROI selection.

Article Snippet: Figure 5 Digital spatial protein immune profiling NanoString GeoMx of treatment-naive PDAC tumors and explorative analysis (A and B) Microscopical images illustrating immunofluorescent staining with morphological markers for PanCK (epithelial tumor cells), CD45 (immune cells), GATA6, and SYTO13 (DNA dye) in treatment-naive tumors.

Techniques: Immunohistochemistry, Staining, Selection

Journal: Cell Reports Medicine

Article Title: GATA6 identifies an immune-enriched phenotype linked to favorable outcomes in patients with pancreatic cancer undergoing upfront surgery

doi: 10.1016/j.xcrm.2024.101557

Figure Lengend Snippet: Digital spatial protein immune profiling NanoString GeoMx of treatment-naive PDAC tumors and explorative analysis (A and B) Microscopical images illustrating immunofluorescent staining with morphological markers for PanCK (epithelial tumor cells), CD45 (immune cells), GATA6, and SYTO13 (DNA dye) in treatment-naive tumors. CD45 expression classified ROIs into areas without immune infiltration (i.e., deserted and CD45 poor) (A) and areas with immune infiltration (i.e., infiltrated and CD45 rich) (B). Both images present three images for each DSP histogroup, illustrating the ROI without segmentation, with the carcinoma (PanCK-rich) and stroma (PanCK-poor) segments. (C‒E) t-SNE biplots illustrating the intra-tumoral expression profiles of 73 proteins in the GeoMx DSP immune-oncology panel in ROIs of treatment-naive patients. Each dot represents an ROI, with coordinates depicting the first (x axis) and second (y axis) t-SNE dimensions. No clustering of ROIs based on the individual patients is observed (C), while apparent clustering is observed based on the histological areas (D). After grouping by GATA6 (E), stroma-infiltrated ROIs showed an apparent clustering pattern, underscoring a possible association between GATA6 and immunological landscapes within this histological context.

Article Snippet: Figure 5 Digital spatial protein immune profiling NanoString GeoMx of treatment-naive PDAC tumors and explorative analysis (A and B) Microscopical images illustrating immunofluorescent staining with morphological markers for PanCK (epithelial tumor cells), CD45 (immune cells), GATA6, and SYTO13 (DNA dye) in treatment-naive tumors.

Techniques: Staining, Expressing

Journal: Cell Reports Medicine

Article Title: GATA6 identifies an immune-enriched phenotype linked to favorable outcomes in patients with pancreatic cancer undergoing upfront surgery

doi: 10.1016/j.xcrm.2024.101557

Figure Lengend Snippet: Digital spatial protein immune profiling NanoString GeoMx analysis of treatment-naive PDAC tumors (A and G) Volcano plots illustrate the DE proteins between GATA6 high and GATA6 low tumors. The x axis displays the log2 fold of change, while the y axis displays the -log10 p .adj. Each dot represents a protein, and protein names indicate that they have exceeded the significance threshold of p .adj < 0.05. Proteins on the right (positive) are overexpressed in GATA6 low tumors, and genes on the left (negative) are overexpressed in GATA6 high tumors. (B‒F) Boxplots illustrating the proportional abundance (y axis) of immune cell subtype markers relative to the general immune cell marker (CD45) in treatment-naive tumors. Notably, CD163 + M2 macrophages are evaluated relative to the total macrophage infiltration marker (CD68). Dual x axes account for disparities in data ranges, with distinct plots associated with the left and right x axes visually separated by the solid black line. The ratios of antigen-presenting cells (CD11c + , HLA-DR + ) (C) and activated T cells (CD27 + , CD8 + ) (D) are significantly lower, while the ratios of CD163 + M2 macrophages (B), regulatory T cells (CD25 + , FOXP3 + ) (E), and CTLA4 + cells (F) are significantly higher in GATA6 low compared to GATA6 high stroma-infiltrated ROIs. The ratios of CD27 + activated T cells and CTLA4 + cells are significantly lower and higher, respectively, in GATA6 low compared to GATA6 high carcinoma-infiltrated ROIs. (H and I) Boxplots illustrating log2 protein expression counts (y axis) of proteins involved in cancer-related processes (H) and proteins involved in apoptotic pathways (I) in the carcinoma segment of treatment-naive tumors. The tumor-promoting fibronectin and MET and BCLXL anti-apoptotic proteins were significantly elevated, and the tumor-suppressing p53 and pro-apoptotic CD95 (Fas) proteins were significantly diminished in GATA6 low compared to GATA6 hgh carcinoma ROIs. In (E)–(K), each dot represents an ROI.

Article Snippet: Figure 5 Digital spatial protein immune profiling NanoString GeoMx of treatment-naive PDAC tumors and explorative analysis (A and B) Microscopical images illustrating immunofluorescent staining with morphological markers for PanCK (epithelial tumor cells), CD45 (immune cells), GATA6, and SYTO13 (DNA dye) in treatment-naive tumors.

Techniques: Marker, Expressing

Journal: Cell Reports Medicine

Article Title: GATA6 identifies an immune-enriched phenotype linked to favorable outcomes in patients with pancreatic cancer undergoing upfront surgery

doi: 10.1016/j.xcrm.2024.101557

Figure Lengend Snippet:

Article Snippet: Figure 5 Digital spatial protein immune profiling NanoString GeoMx of treatment-naive PDAC tumors and explorative analysis (A and B) Microscopical images illustrating immunofluorescent staining with morphological markers for PanCK (epithelial tumor cells), CD45 (immune cells), GATA6, and SYTO13 (DNA dye) in treatment-naive tumors.

Techniques: Activation Assay, Software, Staining

Journal: Scientific Reports

Article Title: Cystic fibrosis-related diabetes is associated with reduced islet protein expression of GLP-1 receptor and perturbation of cell-specific transcriptional programs

doi: 10.1038/s41598-024-76722-1

Figure Lengend Snippet: Spatial transcriptomics analysis of pancreas specimens from subjects in Cohort 2. ( A ) Representative images of islets immunostained for glucagon and insulin that were imaged on the GeoMx Digital Spatial Profiler. ( B ) Principal component analysis for the entire transcriptome of 7 (green) and 5 (pink) glucagon-positive regions of interest in control and CFRD pancreas respectively, and 7 (blue) and 9 (orange) insulin-positive regions of interest in control and CFRD pancreas respectively. Up- (red) and down- (blue) regulated genes in glucagon- ( C ) and insulin- ( D ) positive regions of interest in CFRD vs. control pancreas.

Article Snippet: Figure 4 Spatial transcriptomics analysis of pancreas specimens from subjects in Cohort 2. ( A ) Representative images of islets immunostained for glucagon and insulin that were imaged on the GeoMx Digital Spatial Profiler. ( B ) Principal component analysis for the entire transcriptome of 7 (green) and 5 (pink) glucagon-positive regions of interest in control and CFRD pancreas respectively, and 7 (blue) and 9 (orange) insulin-positive regions of interest in control and CFRD pancreas respectively.

Techniques: Control

Journal: Cancers

Article Title: VISTA Emerges as a Promising Target against Immune Evasion Mechanisms in Medulloblastoma

doi: 10.3390/cancers16152629

Figure Lengend Snippet: The mCB MYC DNp53 mouse medulloblastoma model faithfully recapitulates human disease. ( a ) Transcriptome analysis of 52 human MB patient samples using the Caris Life Sciences database. Quartile expression of IBA-1 transcript (Aif1) was correlated to immune checkpoint and myeloid polarization markers found in our mouse MB model. X -axis represents quartile distribution of IBA-1 transcript expression levels: Q1 (lowest 25%), Q2 (next 25%), Q3 (third 25%), and Q4 (highest 25%). Y -axis represents log2 [TPM+1]. ( b ) Nanostring GeoMx ® Digital spatial profiling performed on a human tissue microarray of MB differential protein expression of immune markers in IBA-positive cells was compared to all other IBA-1-negative cells. Proteins were considered differentially expressed between compared groups with a log2 fold change less than −0.5 or greater than 0.5 and a p -value less than 0.05. In ( a ), error bars represent standard error of the mean (SEM), and p -values were calculated using a Mann–Whitney test and corrected for multiple comparisons. The asterisks indicate adjusted p -values as follows: * padj < 0.05, ** padj < 0.01, *** padj < 0.001, **** padj < 0.0001.

Article Snippet: A single formalin-fixed paraffin-embedded slide containing multiple embryonal human tumor cores in the form of a tissue microarray was stained with 4 immunofluorescent markers, including DAPI, synaptophysin, CD45, and Iba1, and 77 additional proteins from NanoString GeoMx ® Digital Spatial Profiling curated panels, including Immune Cell Profiling, IO Drug Target, Immune Activation Status, PIK/AKT, and Immune Cell Typing panels (NanoString, Seattle, WA, USA).

Techniques: Expressing, Microarray, MANN-WHITNEY