MEN1 deficiency stabilizes PD-L1 and promotes tumor immune evasion of lung cancer.
Cancer Sci
; 115(8): 2515-2527, 2024 Aug.
Article
em En
| MEDLINE
| ID: mdl-38685894
ABSTRACT
Multiple Endocrine Neoplasia 1 gene (MEN1), which is known to be a tumor suppressor gene in lung tissues, encodes a 610 amino acid protein menin. Previous research has proven that MEN1 deficiency promotes the malignant progression of lung cancer. However, the biological role of this gene in the immune microenvironment of lung cancer remains unclear. In this study, we found that programmed cell death-ligand 1 (PD-L1) is upregulated in lung-specific KrasG12D mutation-induced lung adenocarcinoma in mice, after Men1 deficiency. Simultaneously, CD8+ and CD3+ T cells are depleted, and their cytotoxic effects are suppressed. In vitro, PD-L1 is inhibited by the overexpression of menin. Mechanistically, we found that MEN1 inactivation promotes the deubiquitinating activity of COP9 signalosome subunit 5 (CSN5) and subsequently increases the level of PD-L1.
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Base de dados:
MEDLINE
Assunto principal:
Proteínas Proto-Oncogênicas
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Evasão Tumoral
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Antígeno B7-H1
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Neoplasias Pulmonares
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article