Gene-expression profiles of ascites-cytology-positive ovarian cancer
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ABSTRACT: 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.
ORGANISM(S): Homo sapiens
PROVIDER: GSE39204 | GEO | 2012/07/10
SECONDARY ACCESSION(S): PRJNA170198
REPOSITORIES: GEO
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