| 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 | Spatial Transcriptome Analysis of B7-H4 in Head and Neck Squamous Cell Carcinoma: A Novel Therapeutic Target for Anti-Immune Checkpoint Inhibitors. |
| 掲載誌名 | 正式名：Head and neck pathology 略 称：Head Neck Pathol ISSNコード：19360568/1936055X |
| 掲載区分 | 国外 |
| 巻・号・頁 | 19(1),pp.78 |
| 著者・共著者 | Yuri Noda, Masao Yagi, Koji Tsuta |
| 発行年月 | 2025/06 |
| 概要 | PURPOSE:A significant proportion of patients with head and neck squamous cell carcinoma (HNSCC) are ineligible for immune checkpoint inhibitors (ICIs) because of low programmed cell death protein-ligand 1 (PD-L1) expression. The therapeutic potential of B7-H4 (VTCN1) was investigated using immunohistochemistry (IHC) and spatial transcriptomics (ST).METHODS:IHC analysis of B7-H4, PD-L1, CD3, CD4, and CD8 was performed using a tissue microarray [94 HNSCC, 94 adjacent squamous intraepithelial neoplasia (SIN), and 69 adjacent normal oral mucosa (NOM) samples]. B7-H4 and PD-L1 expression levels were assessed using tumor cell score (TC; positive, TC > 1%), immune cell score, and combined positive score. ST was performed on six HNSCCs with paired SINs and NOMs to confirm the expression and distribution of B7-H4 (CTVN1), PD-L1 (CD274), CD4 (DC4A), and CD8 (CD8).RESULTS:In HNSCCs, TCs revealed a mutually exclusive B7-H4/PD-L1 expression pattern in 55% of samples (p < 0.05). B7-H4 positive TCs were more frequent in HNSCCs (79%) than in SINs (10%) and NOMs (2%). ST analysis confirmed mutually exclusive VTCN1/CD274 upregulation in 83% of samples (n = 6) and demonstrated co-localization of B7-H4 protein and VTCN1 in IHC-positive areas. B7-H4 was significantly correlated with low-CD8+ T-cell infiltration (n = 94, p = 0.009), and CD8A mRNA was down-regulated in the VTCN1+ area compared with that in the VTCN1+ area.CONCLUSION:B7-H4 is a promising antibody-drug conjugate target in ICI-resistant HNSCC. IHC combined with TCs enabled the reliable assessment of B7-H4, given its co-localization with VTCN1 in IHC-positive areas and association with low-CD8+ T-cells. |
| DOI | 10.1007/s12105-025-01815-w |
| PMID | 40586978 |