論文 - 詳細
| RRC ID | 71905 |
|---|---|
| 著者 | Kabashima A, Matsuo Y, Ito S, Akiyama Y, Ishii T, Shimada S, Masamune A, Tanabe M, Tanaka S. |
| タイトル | cGAS-STING signaling encourages immune cell overcoming of fibroblast barricades in pancreatic cancer. |
| ジャーナル | Sci Rep |
| Abstract |
Immune checkpoint blockade (ICB) treatment improves the prognosis of several types of solid tumors, however, responsiveness to ICB therapy remains low in pancreatic ductal adenocarcinoma (PDACs), which has a rich tumor microenvironment (TME). The TME is composed of various stromal cells, including cancer-associated fibroblasts (CAFs), which contribute to the establishment of an immunosuppressive microenvironment. The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway is an innate immune pathway that results in the upregulation of immune cell recruiting-cytokines and anti-tumor efficacy. In this study, we aimed to investigate the impact of cGAS-STING expression and the presence of CAFs upon immune cell infiltration in PDACs. cGAS and STING co-expressing PDAC cases showed favorable survival, with many cytotoxic CD8 + T cell infiltrations from the stromal component adjacent to the cancer cells toward cancer cells, but not in cGAS-STING signaling defected PDAC cases. The signatures of tumor-restrain CAFs were expressed in tumors with cGAS-STING signaling. Finally, transwell co-culture experiments demonstrated that immune cell infiltration was impeded by the presence of CAFs, but not by activation of cGAS-STING signaling. In conclusion, pro-infiltration signals, such as cGAS-STING, and characterization of CAFs are crucial in defeating CAF barricades and encouraging immune cell infiltration in PDACs. |
| 巻・号 | 12(1) |
| ページ | 10466 |
| 公開日 | 2022-6-30 |
| DOI | 10.1038/s41598-022-14297-5 |
| PII | 10.1038/s41598-022-14297-5 |
| PMID | 35773436 |
| PMC | PMC9247053 |
| MeSH | Cancer-Associated Fibroblasts* / metabolism Cancer-Associated Fibroblasts* / pathology Carcinoma, Pancreatic Ductal* / metabolism Carcinoma, Pancreatic Ductal* / pathology Humans Membrane Proteins* / metabolism Nucleotidyltransferases* / metabolism Pancreatic Neoplasms* / metabolism Pancreatic Neoplasms* / pathology Signal Transduction Tumor Microenvironment |
| IF | 3.998 |
| 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 | X(Twitter) |
| 各媒体での言及数の合計 | 8 |
| 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 | KLM-1(RCB2138) hPSC-1(RCB3586) |