PD-L1 expression enhancement by infiltrating macrophage-derived tumor necrosis factor-α leads to poor pancreatic cancer prognosis.
Cancer Sci
; 110(1): 310-320, 2019 Jan.
Article
em En
| MEDLINE
| ID: mdl-30426611
ABSTRACT
Immunotherapy using anti-PD-1/PD-L1 antibodies for several types of cancer has received considerable attention in recent decades. However, the molecular mechanism underlying PD-L1 expression in pancreatic ductal adenocarcinoma (PDAC) cells has not been clearly elucidated. We investigated the clinical significance and regulatory mechanism of PD-L1 expression in PDAC cells. Among the various cytokines tested, tumor necrosis factor (TNF)-α upregulated PD-L1 expression in PDAC cells through NF-κB signaling. The induction of PD-L1 expression was also caused by co-culture with activated macrophages, and the upregulation was inhibited by neutralization with anti-TNF-α antibody after co-culture with activated macrophages. PD-L1 expression in PDAC cells was positively correlated with macrophage infiltration in tumor stroma of human PDAC tissues. In addition, survival analysis revealed that high PD-L1 expression was significantly associated with poor prognosis in 235 PDAC patients and especially in patients harboring high CD8-positive T-cell infiltration. These findings indicate that tumor-infiltrating macrophage-derived TNF-α could be a potential therapeutic target for PDAC.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Pancreáticas
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Fator de Necrose Tumoral alfa
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Carcinoma Ductal Pancreático
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Antígeno B7-H1
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Macrófagos
Tipo de estudo:
Prognostic_studies
Limite:
Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Cancer Sci
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Japão