N-MYC impairs innate immune signaling in high-grade serous ovarian carcinoma.
Sci Adv
; 10(20): eadj5428, 2024 May 17.
Article
em En
| MEDLINE
| ID: mdl-38748789
ABSTRACT
High-grade serous ovarian cancer (HGSC) is a challenging disease, especially for patients with immunologically "cold" tumors devoid of tumor-infiltrating lymphocytes (TILs). We found that HGSC exhibits among the highest levels of MYCN expression and transcriptional signature across human cancers, which is strongly linked to diminished features of antitumor immunity. N-MYC repressed basal and induced IFN type I signaling in HGSC cell lines, leading to decreased chemokine expression and T cell chemoattraction. N-MYC inhibited the induction of IFN type I by suppressing tumor cell-intrinsic STING signaling via reduced STING oligomerization, and by blunting RIG-I-like receptor signaling through inhibition of MAVS aggregation and localization in the mitochondria. Single-cell RNA sequencing of human clinical HGSC samples revealed a strong negative association between cancer cell-intrinsic MYCN transcriptional program and type I IFN signaling. Thus, N-MYC inhibits tumor cell-intrinsic innate immune signaling in HGSC, making it a compelling target for immunotherapy of cold tumors.
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Neoplasias Ovarianas
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Transdução de Sinais
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Proteína Proto-Oncogênica N-Myc
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Imunidade Inata
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article