論文 - 詳細
| RRC ID | 78093 |
|---|---|
| 著者 | Sun X, Watanabe T, Oda Y, Shen W, Ahmad A, Ouda R, de Figueiredo P, Kitamura H, Tanaka S, Kobayashi KS. |
| タイトル | Targeted demethylation and activation of NLRC5 augment cancer immunogenicity through MHC class I. |
| ジャーナル | Proc Natl Acad Sci U S A |
| Abstract |
Impaired expression of MHC (major histocompatibility complex) class I in cancers constitutes a major mechanism of immune evasion. It has been well documented that the low level of MHC class I is associated with poor prognosis and resistance to checkpoint blockade therapies. However, there is lmited approaches to specifically induce MHC class I to date. Here, we show an approach for robust and specific induction of MHC class I by targeting an MHC class I transactivator (CITA)/NLRC5, using a CRISPR/Cas9-based gene-specific system, designated TRED-I (Targeted reactivation and demethylation for MHC-I). The TRED-I system specifically recruits a demethylating enzyme and transcriptional activators on the NLRC5 promoter, driving increased MHC class I antigen presentation and accelerated CD8+ T cell activation. Introduction of the TRED-I system in an animal cancer model exhibited tumor-suppressive effects accompanied with increased infiltration and activation of CD8+ T cells. Moreover, this approach boosted the efficacy of checkpoint blockade therapy using anti-PD1 (programmed cell death protein) antibody. Therefore, targeting NLRC5 by this strategy provides an attractive therapeutic approach for cancer. |
| 巻・号 | 121(6) |
| ページ | e2310821121 |
| 公開日 | 2024-2-6 |
| DOI | 10.1073/pnas.2310821121 |
| PMID | 38300873 |
| MeSH | Animals Demethylation Genes, MHC Class I* / genetics Histocompatibility Antigens Class I Neoplasms* / genetics Trans-Activators / metabolism |
| IF | 9.412 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
|
| 最多言及媒体 | News |
| 各媒体での言及数の合計 | 23 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | B16F10(RCB2630) MCF7(RCB1904) |