Unknown,Transcriptomics,Genomics,Proteomics

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Gene-expression profiles of IFN-gamma-affected HOSE cells

ABSTRACT: The source of IFN-Î³ in ovarian cancer microenvironment and its biological effect to the tumor cells is unclear. The immortalized human ovarian surface epithelial cell line, HOSE-E7/hTERT (HOSE) was treated with IFN-Î³ and expression microarray analysis was performed, and probes showing significantly higher values in IFN-Î³-added group were termed â??IFN-Î³ signature genes (295 probes)â??. We then applied this signature to our ovarian cancer microarray data, which included 75 ovarian cancer clinical samples, by means of ss-GSEA. IFN-Î³ signature score was strongly correlated to the number of infiltrating CD4-positive or CD8-positive lymphocytes in the tumors. These data suggest that the IFN-Î³ in the ovarian cancer microenvironment is derived from lymphocytes, and an IFN-Î³-rich microenvironment is strongly correlated to a lymphocyte-rich microenvironment. HOSE cells were incubated in 8 separate culture dishes, 4 dishes with and 4 dishes without 500 IU/ml recombinant human IFN-Î³ (R&D Systems) in the culture medium for 6 hours prior to the analysis.

ORGANISM(S): Homo sapiens

SUBMITTER: Kaoru Abiko

PROVIDER: E-GEOD-55510 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:Glioblastoma multiforme (GBM) is clinically highly aggressive as a result of evolutionary dynamics induced by cross-talk between cancer cells and a heterogeneous group of immune cells in tumor microenvironment. The brain harbors limited numbers of immune cells with few lymphocytes and macrophages; thus, innateâ€like lymphocytes, such as Î³Î´ T cells, have important roles in antitumor immunity. Here, we characterized GBMâ€infiltrating Î³Î´ T cells, which may have roles in regulating the GBM tumor microenvironment and cancer cell gene expression. V(D)J repertoires of tumorâ€infiltrating and bloodâ€circulating Î³Î´ T cells from four patients were analyzed by next-generation sequencing-based T-cell receptor (TCR) sequencing in addition to mutation and immune profiles in four GBM cases. In all tumor tissues, abundant innate and effector/memory lymphocytes were detected, accompanied by large numbers of tumorâ€associated macrophages and closely located tumorâ€infiltrating Î³Î´ T cells, which appear to have anti-tumor activity. The immune-related gene expression analysis using the TCGA database showed that the signature gene expression extent of Î³Î´ T cells were more associated with those of cytotoxic T and Th1 cells and M1 macrophages than those of Th2 cells and M2 macrophages. Although the most abundant Î³Î´ T cells were VÎ³9VÎ´2 T cells in both tumor tissues and blood, the repertoire of intratumoral VÎ³9VÎ´2 T cells was distinct from that of peripheral blood VÎ³9VÎ´2 T cells and was dominated by VÎ³9JÎ³2 sequences, not by canonical VÎ³9JÎ³P sequences that are mostly commonly found in blood Î³Î´ T cells. Collectively, unique GBMâ€specific TCR clonotypes were identified by comparing TCR repertoires of peripheral blood and intraâ€tumoral Î³Î´ T cells. These findings will be helpful for the elucidation of tumor-specific antigens and development of anticancer immunotherapies using tumor-infiltrating Î³Î´ T cells.

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Gene-expression profiles of IFN-gamma-affected HOSE cells

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