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| Status |
Public on Mar 04, 2014 |
| Title |
Gene-expression profiles of ovarian cancer regarding its microenvironment |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
PD-L1 suppresses host immunity and promotes tumor growth. We investigated how IFN-γ regulates PD-L1 in the ovarian cancer microenvironment. In clinical samples, the number of stromal CTLs in peritoneally disseminated tumors was correlated with PD-L1 expression on the tumor cells, and the lymphocyte number was significantly related to the IFN-γ signature score. In mouse models, PD-L1 was induced in peritoneal disseminated tumors, where lymphocytes were prominent, but not in subcutaneous tumors. Depleting IFNGR1 resulted in lower PD-L1 expression and longer survival in peritoneal dissemination model. Injection of IFN-γ into subcutaneous tumors increased PD-L1 expression and tumor size, and PD-L1 depletion abrogated tumor growth. These data suggest that IFN-γ works as a tumor progressor through PD-L1 induction. The source of IFN-γ 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-γ and expression microarray analysis was performed, and probes showing significantly higher values in IFN-γ-added group were termed “IFN-γ signature genes (295 probes)”. We then applied this signature to our ovarian cancer microarray data, which included 75 ovarian cancer clinical samples, by means of ss-GSEA. IFN-γ 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-γ in the ovarian cancer microenvironment is derived from lymphocytes, and an IFN-γ-rich microenvironment is strongly correlated to a lymphocyte-rich microenvironment.
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| Overall design |
Genome-wide transcriptional changes in human ovarian cancer tissue were observed in different tumor immunological microenvironment.
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| Contributor(s) |
Abiko K, Matsumura N |
| Citation(s) |
25867264, 35552285 |
| |
| Submission date |
Mar 03, 2014 |
| Last update date |
Aug 02, 2022 |
| Contact name |
Kaoru Abiko |
| E-mail(s) |
[email protected]
|
| Organization name |
Kyoto University Graduate School of Medicine
|
| Department |
Department of Gynecology and Obstetrics
|
| Street address |
54 Shogoin Kawaharacho, Sakyo-ku
|
| City |
Kyoto |
| ZIP/Postal code |
606-8507 |
| Country |
Japan |
| |
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| Platforms (1) |
| GPL570 |
[HG-U133_Plus_2] Affymetrix Human Genome U133 Plus 2.0 Array |
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| Samples (12)
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| Relations |
| BioProject |
PRJNA239911 |
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