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Status |
Public on Jul 10, 2012 |
Title |
Gene-expression profiles of ascites-cytology-positive ovarian cancer |
Organism |
Homo sapiens |
Experiment type |
Expression profiling by array
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Summary |
Ovarian cancer often progresses by disseminating to the peritoneal cavity, but how the tumor cells evade host immunity during this process is poorly understood. Programmed cell death 1 ligand 1 (PD-L1) is known to suppress immune system and to be an unfavorable prognostic factor in ovarian cancer. The purpose of this study was to elucidate the function of PD-L1 in peritoneal dissemination. Positive cytology in ascites was a significant poor prognostic factor in ovarian cancer. Microarray profiles of cytology-positive cases showed significant correlations with Gene Ontology terms related to immune system process. Microarray and immunohistochemistry in human ovarian cancer revealed significant correlation between PD-L1 expression and positive cytology. PD-L1 expression on mouse ovarian cancer cells was induced upon encountering lymphocytes in the course of peritoneal spread in vivo and upon co-culturing with lymphocytes in vitro. Tumor cell lysis by CTLs was attenuated when PD-L1 was overexpressed and promoted when it was silenced. PD-L1 overexpression also inhibited gathering and degranulation of CTLs. In mouse ovarian cancer dissemination models, depleting PD-L1 expression on tumor cells resulted in inhibited tumor growth in the peritoneal cavity and prolonged survival. Restoring immune function by inhibiting immune-suppressive factors such as PD-L1 may be a promising therapeutic strategy for peritoneal dissemination.
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Overall design |
Genome-wide transcriptional changes in human ovarian cancer tissue from ascites-cytology-positive or -negative patients.
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Contributor(s) |
Abiko K, Mandai M |
Citation(s) |
23340297, 35552285 |
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Submission date |
Jul 09, 2012 |
Last update date |
Aug 02, 2022 |
Contact name |
Kaoru Abiko |
E-mail(s) |
[email protected]
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Organization name |
Kyoto University Graduate School of Medicine
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Department |
Department of Gynecology and Obstetrics
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Street address |
54 Shogoin Kawaharacho, Sakyo-ku
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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 (64)
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Relations |
BioProject |
PRJNA170198 |