論文 - 詳細
| RRC ID | 78697 |
|---|---|
| 著者 | Ye J, Suizu F, Yamakawa K, Mukai Y, Kato M, Yoneyama H, Yahagi N, Matsuda Y. |
| タイトル | Silencing of tumoral carbohydrate sulfotransferase 15 reactivates lymph node pancreatic cancer T cells in mice. |
| ジャーナル | Eur J Immunol |
| Abstract |
Limited intratumoral T-cell infiltration in pancreatic ductal adenocarcinoma (PDAC) is an obstacle to immunotherapy, yet the efficient approach to enhance tumor-infiltrating T cells is not fully established. Here, we show that tumor-specific knockdown of carbohydrate sulfotransferase 15 (CHST15), a tumor stromal proteoglycan-synthetic enzyme, suppresses tumor growth in a T-cell-dependent manner in a murine model of PDAC. Silencing of tumoral CHST15 unexpectedly expanded CD4+ and CD8+ T cells in tumor draining LN (TDLN), leading to accelerated accumulation of EdU+ proliferating CD4+ and CD8+ T cells and granzyme B+ CD8+ T cells in the tumor. RNA expression analysis indicated that tumoral CHST15 knockdown (KD) downregulated matrix remodeling-related genes, while upregulated anti-tumor T-cell activity-related genes in both tumor and TDLN. CHST15 KD significantly diminished intratumoral and TDLN Ly6C/G+ myeloid-derived suppressor cells prior to TDLN T-cell expansion, suggesting that tumoral CHST15 remotely regulated myeloid-derived suppressor cell mediated T-cell suppression in the TDLN. Our findings illustrate a novel immunotherapeutic potential of tumoral CHST15 blockage by reactivating T cells in immune suppressive TDLN of PDAC. |
| 巻・号 | 53(9) |
| ページ | e2250160 |
| 公開日 | 2023-9-1 |
| DOI | 10.1002/eji.202250160 |
| PMID | 37248998 |
| MeSH | Animals CD8-Positive T-Lymphocytes Carbohydrate Sulfotransferases Carcinoma, Pancreatic Ductal* / genetics Carcinoma, Pancreatic Ductal* / metabolism Lymph Nodes Lymphoma* Mice Mice, Inbred C57BL Pancreatic Neoplasms* / genetics |
| IF | 4.404 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | Peer-review(Publons) |
| 各媒体での言及数の合計 | 5 |
| 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 | CTLL-2(RCB0637) |