The influence of clinical risk factors on the classification of human cancer-associated fibroblasts in PDAC and pancreatitis patients
Abstract Cancer-associated fibroblasts (CAFs) constitute an important cell population in the microenvironment of pancreatic cancer. They can arise from disease-associated fibroblasts (DAFs) to support or restrain tumor growth. How many CAF subtypes exist and what signals drive their development is u...
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Nature Portfolio
2025-06-01
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| Series: | BJC Reports |
| Online Access: | https://doi.org/10.1038/s44276-025-00150-5 |
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| author | Viktoria Boeker Lena Wilke Ana Mansourkiaei Van Manh H. Le Kaira A. Church Zoltan Czigany Bo Kong Fernanda G. Kugeratski Jörg Kleeff Jürgen Weitz Christoph Kahlert |
| author_facet | Viktoria Boeker Lena Wilke Ana Mansourkiaei Van Manh H. Le Kaira A. Church Zoltan Czigany Bo Kong Fernanda G. Kugeratski Jörg Kleeff Jürgen Weitz Christoph Kahlert |
| author_sort | Viktoria Boeker |
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| description | Abstract Cancer-associated fibroblasts (CAFs) constitute an important cell population in the microenvironment of pancreatic cancer. They can arise from disease-associated fibroblasts (DAFs) to support or restrain tumor growth. How many CAF subtypes exist and what signals drive their development is unclear. Currently, there are three commonly accepted subtypes, namely myofibroblast-like (myCAF), immunomodulatory (iCAF), and antigen-presenting (apCAF). Here, we analyzed the correlation between clinical risk factors with the proportion of each CAF subtype. In our patient cohort (n = 21), we investigated DAFs from patients with chronic pancreatitis (CP) and CAFs from pancreatic ductal adenocarcinoma (PDAC) patients after surgical resection via flow cytometry and RNA expression analysis. The expression of iCAF marker Interleukin-6 displayed significant differences depending on lifestyle factors, such as smoking status, age, and Body Mass Index (BMI). The apCAF marker HLA-DQA1 correlated with age. The largest difference showed the quantitative difference of apCAF markers in ~40% of PDAC- and ~20% of CP patients. In conclusion, clinical risk factors may influence the prevelance of specific CAF subsets. Unraveling the complex interplay between CAFs and tumor cells is crucial for novel therapies to improve long-term survival for pancreatic cancer patients. |
| format | Article |
| id | doaj-art-77b4c20cd7a54632b498a39cbb5a7247 |
| institution | Kabale University |
| issn | 2731-9377 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | BJC Reports |
| spelling | doaj-art-77b4c20cd7a54632b498a39cbb5a72472025-08-20T03:47:24ZengNature PortfolioBJC Reports2731-93772025-06-013111010.1038/s44276-025-00150-5The influence of clinical risk factors on the classification of human cancer-associated fibroblasts in PDAC and pancreatitis patientsViktoria Boeker0Lena Wilke1Ana Mansourkiaei2Van Manh H. Le3Kaira A. Church4Zoltan Czigany5Bo Kong6Fernanda G. Kugeratski7Jörg Kleeff8Jürgen Weitz9Christoph Kahlert10Department of Visceral, Thoracic and Vascular Surgery, University Medical Center Carl Gustav Carus DresdenDepartment of Visceral, Thoracic and Vascular Surgery, University Medical Center Carl Gustav Carus DresdenDepartment of General-, Visceral-, and Transplant Surgery, Ruprecht Karl University Heidelberg, University Medical Center HeidelbergDepartment of General-, Visceral-, and Transplant Surgery, Ruprecht Karl University Heidelberg, University Medical Center HeidelbergDepartment of Cancer Biology, University of Texas MD Anderson Cancer CenterDepartment of General-, Visceral-, and Transplant Surgery, Ruprecht Karl University Heidelberg, University Medical Center HeidelbergDepartment of General-, Visceral-, and Transplant Surgery, Ruprecht Karl University Heidelberg, University Medical Center HeidelbergDepartment of Experimental Therapeutics, University of Texas MD Anderson Cancer CenterDepartment of Visceral, Vascular and Endocrine Surgery, Martin-Luther-University Halle-Wittenberg, University Medical Center HalleDepartment of Visceral, Thoracic and Vascular Surgery, University Medical Center Carl Gustav Carus DresdenDepartment of General-, Visceral-, and Transplant Surgery, Ruprecht Karl University Heidelberg, University Medical Center HeidelbergAbstract Cancer-associated fibroblasts (CAFs) constitute an important cell population in the microenvironment of pancreatic cancer. They can arise from disease-associated fibroblasts (DAFs) to support or restrain tumor growth. How many CAF subtypes exist and what signals drive their development is unclear. Currently, there are three commonly accepted subtypes, namely myofibroblast-like (myCAF), immunomodulatory (iCAF), and antigen-presenting (apCAF). Here, we analyzed the correlation between clinical risk factors with the proportion of each CAF subtype. In our patient cohort (n = 21), we investigated DAFs from patients with chronic pancreatitis (CP) and CAFs from pancreatic ductal adenocarcinoma (PDAC) patients after surgical resection via flow cytometry and RNA expression analysis. The expression of iCAF marker Interleukin-6 displayed significant differences depending on lifestyle factors, such as smoking status, age, and Body Mass Index (BMI). The apCAF marker HLA-DQA1 correlated with age. The largest difference showed the quantitative difference of apCAF markers in ~40% of PDAC- and ~20% of CP patients. In conclusion, clinical risk factors may influence the prevelance of specific CAF subsets. Unraveling the complex interplay between CAFs and tumor cells is crucial for novel therapies to improve long-term survival for pancreatic cancer patients.https://doi.org/10.1038/s44276-025-00150-5 |
| spellingShingle | Viktoria Boeker Lena Wilke Ana Mansourkiaei Van Manh H. Le Kaira A. Church Zoltan Czigany Bo Kong Fernanda G. Kugeratski Jörg Kleeff Jürgen Weitz Christoph Kahlert The influence of clinical risk factors on the classification of human cancer-associated fibroblasts in PDAC and pancreatitis patients BJC Reports |
| title | The influence of clinical risk factors on the classification of human cancer-associated fibroblasts in PDAC and pancreatitis patients |
| title_full | The influence of clinical risk factors on the classification of human cancer-associated fibroblasts in PDAC and pancreatitis patients |
| title_fullStr | The influence of clinical risk factors on the classification of human cancer-associated fibroblasts in PDAC and pancreatitis patients |
| title_full_unstemmed | The influence of clinical risk factors on the classification of human cancer-associated fibroblasts in PDAC and pancreatitis patients |
| title_short | The influence of clinical risk factors on the classification of human cancer-associated fibroblasts in PDAC and pancreatitis patients |
| title_sort | influence of clinical risk factors on the classification of human cancer associated fibroblasts in pdac and pancreatitis patients |
| url | https://doi.org/10.1038/s44276-025-00150-5 |
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