Immuno-Oncologic Profiling by Stage-Dependent Transcriptome and Proteome Analyses of Spontaneously Regressing Canine Cutaneous Histiocytoma
Ontology highlight
ABSTRACT:
INSTRUMENT(S): ultrafleXtreme, Q Exactive HF
ORGANISM(S): Canis Lupus Familiaris (ncbitaxon:9615)
SUBMITTER: 
Benjamin-Florian Hempel
PROVIDER: MSV000094245 | MassIVE | Wed Mar 06 06:04:00 GMT 2024
SECONDARY ACCESSION(S): PXD050403
REPOSITORIES: MassIVE
Similar Datasets
Project description:Canine cutaneous histiocytoma (CCH) is a tumor originating from dermal Langerhans cells, especially affecting young dogs. The common spontaneous regression of CCH makes it an interesting model in comparative oncology research. Previous studies have indicated that anti-tumor immune responses may be involved but details remain speculative to date. Here, we asked which specific immuno-oncological dynamics underlie spontaneous regression of CCH on mRNA and protein levels. QuantSeq 3' mRNA sequencing with functional overrepresentation analysis and an nCounter RNA hybridization assay were employed on 21 formalin-fixed, paraffin-embedded CCH samples representing three different tumor stages. Nine additional samples were subjected to matrix-assisted laser desorption ionization mass spectrometry imaging (MALDI-MSI). Surprisingly, only minor stage-specific differences were found. When we investigated expression of B7 family ligands and CD28 family receptors holding co-stimulatory and -inhibitory functions respectively, we found higher abundance of CD80, CD86 and CD28, which trigger activation of lymphocyte-mediated immune responses. CD80 and CD86 expressing cells were further quantified by in situ hybridization and compared with data from three cases of canine histiocytic sarcoma (HS), a malignant tumor variant originating from antigen presenting cells. A stage-specific increase of CD80 expression was recorded in CCH from the tumor bottom to the top, while CD86 was continuously and homogenously expressed at high levels. Expression of CD80 in CCH was similar to that in HS (73.3 ± 37.4% versus 62.1 ± 46.4% positive cells), while CD86 was significantly higher expressed in CCH (94.7 ± 10.3%) when compared to HS (57.6 ± 11.0%). Our data suggest that major immuno-oncological pathways are seemingly not regulated during regression of CCH on the mRNA or protein levels as detectable by the methods used. We speculate that key signals leading to tumor regression may occur at an interactome level or at an earlier time point than examined here. Our data further supports a role of immune stimulatory B7 family ligands and CD28 family receptors in CCH regression.
2024-04-10 | GSE261395 | GEO
Project description:Canine cutaneous histiocytoma (CCH) is a tumor originating from dermal Langerhans cells, especially affecting young dogs. The common spontaneous regression of CCH makes it an interesting model in comparative oncology research. Previous studies have indicated that anti-tumor immune responses may be involved but details remain speculative to date. Here, we asked which specific immuno-oncological dynamics underlie spontaneous regression of CCH on mRNA and protein levels. QuantSeq 3' mRNA sequencing with functional overrepresentation analysis and an nCounter RNA hybridization assay were employed on 21 formalin-fixed, paraffin-embedded CCH samples representing three different tumor stages. Nine additional samples were subjected to matrix-assisted laser desorption ionization mass spectrometry imaging (MALDI-MSI). Surprisingly, only minor stage-specific differences were found. When we investigated expression of B7 family ligands and CD28 family receptors holding co-stimulatory and -inhibitory functions respectively, we found higher abundance of CD80, CD86 and CD28, which trigger activation of lymphocyte-mediated immune responses. CD80 and CD86 expressing cells were further quantified by in situ hybridization and compared with data from three cases of canine histiocytic sarcoma (HS), a malignant tumor variant originating from antigen presenting cells. A stage-specific increase of CD80 expression was recorded in CCH from the tumor bottom to the top, while CD86 was continuously and homogenously expressed at high levels. Expression of CD80 in CCH was similar to that in HS (73.3 ± 37.4% versus 62.1 ± 46.4% positive cells), while CD86 was significantly higher expressed in CCH (94.7 ± 10.3%) when compared to HS (57.6 ± 11.0%). Our data suggest that major immuno-oncological pathways are seemingly not regulated during regression of CCH on the mRNA or protein levels as detectable by the methods used. We speculate that key signals leading to tumor regression may occur at an interactome level or at an earlier time point than examined here. Our data further supports a role of immune stimulatory B7 family ligands and CD28 family receptors in CCH regression.
2024-04-10 | GSE261387 | GEO
Project description:Canine cutaneous histiocytoma (CCH) is a tumor originating from dermal Langerhans cells, especially affecting young dogs. The common spontaneous regression of CCH makes it an interesting model in comparative oncology research. Previous studies have indicated that anti-tumor immune responses may be involved but details remain speculative to date. Here, we asked which specific immuno-oncological dynamics underlie spontaneous regression of CCH on mRNA and protein levels. QuantSeq 3' mRNA sequencing with functional overrepresentation analysis and an nCounter RNA hybridization assay were employed on 21 formalin-fixed, paraffin-embedded CCH samples representing three different tumor stages. Nine additional samples were subjected to matrix-assisted laser desorption ionization mass spectrometry imaging (MALDI-MSI). Surprisingly, only minor stage-specific differences were found. When we investigated expression of B7 family ligands and CD28 family receptors holding co-stimulatory and -inhibitory functions respectively, we found higher abundance of CD80, CD86 and CD28, which trigger activation of lymphocyte-mediated immune responses. CD80 and CD86 expressing cells were further quantified by in situ hybridization and compared with data from three cases of canine histiocytic sarcoma (HS), a malignant tumor variant originating from antigen presenting cells. A stage-specific increase of CD80 expression was recorded in CCH from the tumor bottom to the top, while CD86 was continuously and homogenously expressed at high levels. Expression of CD80 in CCH was similar to that in HS (73.3 ± 37.4% versus 62.1 ± 46.4% positive cells), while CD86 was significantly higher expressed in CCH (94.7 ± 10.3%) when compared to HS (57.6 ± 11.0%). Our data suggest that major immuno-oncological pathways are seemingly not regulated during regression of CCH on the mRNA or protein levels as detectable by the methods used. We speculate that key signals leading to tumor regression may occur at an interactome level or at an earlier time point than examined here. Our data further supports a role of immune stimulatory B7 family ligands and CD28 family receptors in CCH regression. Attention: this GEO submission includes the nCounter® data from 10 of the 35 samples used in this study! The data from 3' RNA-Seq (QuantSeq 3') and the other entety-contrasting 25 tumour samples were submitted separately to GEO.
2024-03-21 | GSE262020 | GEO
Project description:Spontaneous regression is a well defined phenomenon commonly observed in human melanoma in its partial histopathological form but sporadically in its complete expression. Molecular mechanisms which might be involved in spontaneous regression are poorly understood so far. The Melanoblastoma bearing Libechov Minipig (MeLiM) model exhibits cutaneous melanomas which appear in utero or shortly after birth. These lesions are clinically and histologically highly comparable to their human counterparts. Nevertheless, in swine most of the highly invasive melanomas undergo complete spontaneous regression. Induction of regression is expressed by clinical features including changes in color, drying aspect and decrease in size; histologically we observed infiltration of histiocyte-like cells, fibrosis and lymphocytic infiltrate later. To characterize the regression phase on a transciptomic level, we performed time dependent gene expression profiling using the MeLiM model and porcine Affymetrix microarrays. We collected 5 different tumors of 5 siblings at 5 timepoints, from day 8 to day 91 after birth. After statistical analysis and reannotation of the 25 porcine microarrays we were able to identify 1411 genes regulated during regression. K-means clustering and subsequent functional clustering of these genes via Ingenuity Pathway analysis revealed significant pathways playing a role in melanoma regression. Genes involved in cell cycle, apoptosis, cellular movement, melanocyte-differentiation and pigmentation as well as genes of the immune reponse seem to be potential mediators of melanoma regression.
2008-09-10 | E-MEXP-1152 | biostudies-arrayexpress
Project description:The purpose of this study was to treat cutaneous melanoma metastases with topical DPCP, and then to comprehensively study the induced immune responses associated with tumor regression.
2016-06-02 | GSE82105 | GEO
Project description:Spontaneous tumor regression is driven by Wnt/Retinoic Acid signaling cross-talk
| PRJNA235185 | ENA
Project description:Numerous case studies have reported spontaneous regression of metastases following tumor excision, but underlying mechanisms are elusive. Here we present a model of metastases regression and latency elicited by the removal of a primary tumor, and identify underlying mechanisms. Human breast cancer cells, expressing highly sensitive luciferase, were implanted into the mammary fat-pad of mice, and the progression of early stage micrometastases, was monitored. Upon establishment of micrometastases, the primary tumor was excised, inducing a robust regression of metastatic signal, resulting in latent foci. In vivo supplementation of tumor secretome immediately upon tumor excision diminished this regression, implicating primary tumor secreted factors in promotion of metastatic growth. In vitro, cancer cell conditioned medium reduced apoptosis and enhanced adhesion of non-confluent cancer cells, and induced angiogenesis in endothelial cells. Cytokine array and proteomic analysis of cancer cells secretome identified 359 extracellular secreted factors, with significant enrichment of angiogenic factors, growth factors activity, focal adhesion, apoptosis, and metalloprotease processes. In vivo blockade of four key potential mediators of these processes, IL-8, PDGFaa, Serpin E1 (PAI-1), and MIF, arrested development of micrometastases. Moreover, high protein levels of these four factors were correlated with poor patient outcome. These results demonstrate regression and latency of metastases following tumor excision and a crucial role for primary tumor secretome in promoting early metastatic stages, suggesting novel mechanisms to control minimal residual disease.
2020-10-07 | PXD008384 | Pride
Project description:We report sequencing of 10 localized and 10 metastatic cutaneous squamous cell carcinomas from human subjects. Sequencing was done on an oncology targeted gene mutation panel consisting of 76 genes.
2020-07-15 | GSE150727 | GEO
Project description:Colorectal cancer, one of the most frequent types of malignancy in the Western world, develops through a multi-step process. The main pathways establishing transformation of normal mucosa to invasive carcinoma include chromosomal instability (CIN), microsatellite instability (MSI) or epigenetic silencing through the CpG Island Methylator Phenotype (CIMP). These pathways have distinct clinical, pathological and genetic characteristics. In general, altered cell surface glycosylation has been linked to colorectal cancer progression, however the impact of MSI-specific pathways on the glycosylation machinery of MSI colon cancer cells has not been investigated yet. In a recent study (Patsos et al., 2009) we have shown that MSI-specific mutations induce marked alterations in cell surface glycosylation, indicating specific changes in the expression of glyco-genes. Therefore the purpose of our experiment is to define these changes by glyco-gene chip analysis. Biallelic mutational inactivation of MSI target genes is believed to drive MSI tumorigenesis. TGFBR2, ACVR2 and AIM2 are among the most frequently mutated genes in MSI colorectal adenomas and carcinomas and functional studies indicate their contribution to MSI-carcinogenesis. A first general screening approach by lectin FACS analysis indicated a correlation between functional inactivation of these genes and cell surface glycosylation of the MSI colon cell line HCT116 (Patsos et al., 2009). For detailed analysis of the altered glycosylation pattern and the underlying molecular mechanisms we have established HCT116 double stable transfectants that allow doxycycline-inducible expression of the three MSI target genes TGFBR2, ACVR2 and AIM2 in a reversible manner. Thus we can experimentally control the expression of the MSI-genes and analyze short and long-term effects on different cell functions, including glycosylation. From the application of the glyco-gene chip for analysis of the transfectants we expect to gain seminal information on the influence of MSI-target genes on glycan expression and function in MSI tumor cells. Correlating loss-of-function of MSI target genes not yet linked with glycosylation to the regulation of the glycophenotype is a novel approach to investigate the glycobiology of tumor cells. In addition it is also suitable to detect new MSI-(glyco)markers for clinical applications, including diagnostic tumor markers and specific targets for immunotherapies.
2011-09-05 | E-GEOD-31927 | biostudies-arrayexpress
Project description:Genomic instability, including microsatellite instability (MSI) and gross chromosomal abnormalities, has been described in sporadic colorectal cancer (CRC) and MSI has been suggested to have prognostic significance. However, there are few prognostically relevant biomarkers. Here we explore the potential of the analysis of DNA copy number changes at 1Mb resolution to predict survivorship in sporadic CRC. Keywords: Comparative Genomic Hybridization
2010-02-11 | GSE12520 | GEO