| 論文種別 | 原著(症例報告除く) |
| 言語種別 | 英語 |
| 査読の有無 | その他(不明) |
| 表題 | AGTR1 signaling contributes to tumor immunity and therapy response in non-small cell lung cancer. |
| 掲載誌名 | 正式名：Molecular therapy. Oncology 略 称：Mol Ther Oncol ISSNコード：29503299/29503299 |
| 掲載区分 | 国外 |
| 巻・号・頁 | 34(3),pp.201253 |
| 著者・共著者 | Tatsuki Ikoma, Keigo Araki, Mai Kitagawa, Natsuno Makihara, Yutaro Nagata, Kazuki Fujii, Yukiko Okuno, Keisuke Kamisako, Yuta Okazaki, Kentaro Nakanishi, Yume Sanada, Kiyori Yoshida, Kahori Nakahama, Yuki Takeyasu, Utae Katsushima, Yuta Yamanaka, Satoshi Ikeda, Hiroshige Yoshioka, Toshio Shimizu, Takayasu Kurata |
| 発行年月 | 2026/05 |
| 概要 | Angiotensin II receptor type 1 (AGTR1) has emerged as a potential modulator of the tumor microenvironment, yet its role in the immunotherapy response in non-small cell lung cancer (NSCLC) remains unclear. We performed a comprehensive analysis using bulk RNA sequencing and single-cell RNA sequencing (scRNA-seq) datasets. Functional validation included IHC for AGTR1 and phospho-SMAD2/3 co-localization. The clinical impact of angiotensin receptor blocker (ARB) use was assessed in patients receiving immune checkpoint blockade (ICB) alone or combined with chemo-immunotherapy. AGTR1-high expression in NSCLC was associated with pronounced pathway modulation, including significant upregulation of TGF-β, etc. scRNA-seq analysis revealed that AGTR1 was predominantly localized in cancer-associated fibroblasts (CAFs). IHC validation in NSCLC specimens (n = 14) demonstrated a strong correlation between stromal AGTR1 and phospho-SMAD2/3 expression and ARB-treated patients showed significantly reduced stromal AGTR1 and pSMAD2/3 expression. Clinically, ARB treatment showed no benefit in ICB monotherapy but significantly improved PFS in chemo-immunotherapy (HR = 0.70, p = 0.01), especially in non-squamous (non-Sq) histology with PD-L1≥1% (HR = 0.52, p = 0.01). AGTR1 is predominantly expressed in CAFs and is suggestive of a correlation with TGF-β-related immunosuppressive features in NSCLC. The combination of ARB with chemo-immunotherapy may enhance therapeutic efficacy through targeting that axis in CAFs, specifically in non-Sq NSCLC patients. |
| DOI | 10.1016/j.omton.2026.201253 |
| PMID | 42368624 |