The Crosstalk with CXCL10‐Rich Tumor‐Associated Mast Cells Fuels Pancreatic Cancer Progression and Immune Escape
Abstract Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease, necessitating approaches to improve prognosis. As the mediator of allergic process, mast cells have been found in various cancers and are associated with survival. However, the biological behaviors of tumor‐associated mast ce...
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Wiley
2025-04-01
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| Online Access: | https://doi.org/10.1002/advs.202417724 |
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| author | Hanlin Yin Qiangda Chen Shanshan Gao Sami Shoucair Yuqi Xie Joseph R. Habib Taochen He Wei Gan Juan Wang Lei Zhang Huaxiang Xu Chenye Shi Junyi He Wenquan Wang Yun Jin Michael G Goggins Liang Liu Wenhui Lou Wenchuan Wu Jun Yu Ning Pu |
| author_facet | Hanlin Yin Qiangda Chen Shanshan Gao Sami Shoucair Yuqi Xie Joseph R. Habib Taochen He Wei Gan Juan Wang Lei Zhang Huaxiang Xu Chenye Shi Junyi He Wenquan Wang Yun Jin Michael G Goggins Liang Liu Wenhui Lou Wenchuan Wu Jun Yu Ning Pu |
| author_sort | Hanlin Yin |
| collection | DOAJ |
| description | Abstract Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease, necessitating approaches to improve prognosis. As the mediator of allergic process, mast cells have been found in various cancers and are associated with survival. However, the biological behaviors of tumor‐associated mast cells (TAMCs) remain unclear. Herein, an excessive infiltration of TAMCs in PDAC is demonstrated, which apparently associated with poor survival in PDAC patients. PDAC cells are found to recruit CXCR2+ MCs into TME, and then inhibited MCs ferroptosis, and maintained their proliferation. Concomitantly, the tumor‐derived exosome miR‐188‐5p activated the PTEN/AKT/GSK3β signaling, further stabilized transcriptional factor ERG by inhibiting its ubiquitin degradation, and finally enhanced the transcription of cxcl10 within TAMCs. In reverse, TAMCs‐derived CXCL10 reversely promoted tumor epithelial‐mesenchymal transition and induced immunosuppressive tumor microenvironment by recruiting CXCR3+ Tregs. Sodium cromoglycate (SCG) is a membrane stabilizer for MCs and confirmed as an effective and widely used agent to block TAMCs‐derived CXCL10 and further sensitize the therapeutic efficacy of anti‐PD‐1 antibody plus gemcitabine for PDAC. These findings illuminate a critical and innovative crosstalk between TAMCs and PDAC cells that promote PDAC progression, and SCG sensitizes PDAC to the current immuno‐chemotherapy, which reveals its potential to be a valuable adjuvant for PDAC patients. |
| format | Article |
| id | doaj-art-e0952a217c6b4a23aeafb384b840072b |
| institution | DOAJ |
| issn | 2198-3844 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj-art-e0952a217c6b4a23aeafb384b840072b2025-08-20T03:09:08ZengWileyAdvanced Science2198-38442025-04-011214n/an/a10.1002/advs.202417724The Crosstalk with CXCL10‐Rich Tumor‐Associated Mast Cells Fuels Pancreatic Cancer Progression and Immune EscapeHanlin Yin0Qiangda Chen1Shanshan Gao2Sami Shoucair3Yuqi Xie4Joseph R. Habib5Taochen He6Wei Gan7Juan Wang8Lei Zhang9Huaxiang Xu10Chenye Shi11Junyi He12Wenquan Wang13Yun Jin14Michael G Goggins15Liang Liu16Wenhui Lou17Wenchuan Wu18Jun Yu19Ning Pu20Department of Pancreatic Surgery Zhongshan Hospital Fudan University Shanghai 200032 ChinaDepartment of Pancreatic Surgery Zhongshan Hospital Fudan University Shanghai 200032 ChinaDepartment of Radiology Zhongshan Hospital Fudan University Shanghai 200032 ChinaDepartments of Medicine, Oncology and Surgery Johns Hopkins University School of Medicine Baltimore MD 21287 USADepartment of Pancreatic Surgery Zhongshan Hospital Fudan University Shanghai 200032 ChinaDepartment of Surgery New York University School of Medicine and NYU‐Langone Medical Center New York NY 10016 USADepartment of Pancreatic Surgery Zhongshan Hospital Fudan University Shanghai 200032 ChinaDepartment of Pancreatic Surgery Zhongshan Hospital Fudan University Shanghai 200032 ChinaHANGZHOU CHEXMED TECHNOLOGY CO., LTD Hangzhou 310000 ChinaDepartment of Pancreatic Surgery Zhongshan Hospital Fudan University Shanghai 200032 ChinaDepartment of Pancreatic Surgery Zhongshan Hospital Fudan University Shanghai 200032 ChinaDepartment of Pancreatic Surgery Zhongshan Hospital Fudan University Shanghai 200032 ChinaDepartment of Pancreatic Surgery Zhongshan Hospital Fudan University Shanghai 200032 ChinaDepartment of Pancreatic Surgery Zhongshan Hospital Fudan University Shanghai 200032 ChinaDepartment of Hepatobiliary and Pancreatic Surgery The First People's Hospital of Yunnan Province The Affiliated Hospital of Kunming University of Science and Technology Kunming 650500 ChinaDepartments of Medicine and Pathology The Sol Goldman Pancreatic Cancer Research Center Johns Hopkins University School of Medicine Baltimore MD 21287 USADepartment of Pancreatic Surgery Zhongshan Hospital Fudan University Shanghai 200032 ChinaDepartment of Pancreatic Surgery Zhongshan Hospital Fudan University Shanghai 200032 ChinaDepartment of Pancreatic Surgery Zhongshan Hospital Fudan University Shanghai 200032 ChinaDepartments of Medicine, Oncology and Surgery Johns Hopkins University School of Medicine Baltimore MD 21287 USADepartment of Pancreatic Surgery Zhongshan Hospital Fudan University Shanghai 200032 ChinaAbstract Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease, necessitating approaches to improve prognosis. As the mediator of allergic process, mast cells have been found in various cancers and are associated with survival. However, the biological behaviors of tumor‐associated mast cells (TAMCs) remain unclear. Herein, an excessive infiltration of TAMCs in PDAC is demonstrated, which apparently associated with poor survival in PDAC patients. PDAC cells are found to recruit CXCR2+ MCs into TME, and then inhibited MCs ferroptosis, and maintained their proliferation. Concomitantly, the tumor‐derived exosome miR‐188‐5p activated the PTEN/AKT/GSK3β signaling, further stabilized transcriptional factor ERG by inhibiting its ubiquitin degradation, and finally enhanced the transcription of cxcl10 within TAMCs. In reverse, TAMCs‐derived CXCL10 reversely promoted tumor epithelial‐mesenchymal transition and induced immunosuppressive tumor microenvironment by recruiting CXCR3+ Tregs. Sodium cromoglycate (SCG) is a membrane stabilizer for MCs and confirmed as an effective and widely used agent to block TAMCs‐derived CXCL10 and further sensitize the therapeutic efficacy of anti‐PD‐1 antibody plus gemcitabine for PDAC. These findings illuminate a critical and innovative crosstalk between TAMCs and PDAC cells that promote PDAC progression, and SCG sensitizes PDAC to the current immuno‐chemotherapy, which reveals its potential to be a valuable adjuvant for PDAC patients.https://doi.org/10.1002/advs.202417724CXCL10immune escapepancreatic ductal adenocarcinomasodium cromoglycatetumor‐associated mast cell |
| spellingShingle | Hanlin Yin Qiangda Chen Shanshan Gao Sami Shoucair Yuqi Xie Joseph R. Habib Taochen He Wei Gan Juan Wang Lei Zhang Huaxiang Xu Chenye Shi Junyi He Wenquan Wang Yun Jin Michael G Goggins Liang Liu Wenhui Lou Wenchuan Wu Jun Yu Ning Pu The Crosstalk with CXCL10‐Rich Tumor‐Associated Mast Cells Fuels Pancreatic Cancer Progression and Immune Escape Advanced Science CXCL10 immune escape pancreatic ductal adenocarcinoma sodium cromoglycate tumor‐associated mast cell |
| title | The Crosstalk with CXCL10‐Rich Tumor‐Associated Mast Cells Fuels Pancreatic Cancer Progression and Immune Escape |
| title_full | The Crosstalk with CXCL10‐Rich Tumor‐Associated Mast Cells Fuels Pancreatic Cancer Progression and Immune Escape |
| title_fullStr | The Crosstalk with CXCL10‐Rich Tumor‐Associated Mast Cells Fuels Pancreatic Cancer Progression and Immune Escape |
| title_full_unstemmed | The Crosstalk with CXCL10‐Rich Tumor‐Associated Mast Cells Fuels Pancreatic Cancer Progression and Immune Escape |
| title_short | The Crosstalk with CXCL10‐Rich Tumor‐Associated Mast Cells Fuels Pancreatic Cancer Progression and Immune Escape |
| title_sort | crosstalk with cxcl10 rich tumor associated mast cells fuels pancreatic cancer progression and immune escape |
| topic | CXCL10 immune escape pancreatic ductal adenocarcinoma sodium cromoglycate tumor‐associated mast cell |
| url | https://doi.org/10.1002/advs.202417724 |
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