Fibroblast heterogeneity in pancreatic ductal adenocarcinoma: Perspectives in immunotherapy |
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| Institution: | 1. Centre of Reproduction, Development and Aging and Institute of Translation Medicine, Faculty of Health Sciences, University of Macau, Macau 999078, China;2. Brain Research Centre and Department of Biology, School of Life Science, Southern University of Science and Technology, 1088 Xueyuan Blvd, Nanshan District, Shenzhen, Guangdong Province 518055, China;3. Allergy and Clinical Immunology Unit, Department of Medicine, Hadassah-Hebrew University Medical Center, Jerusalem 9112001, Israel;4. Anesthesia, Critical Care Medicine and Physiology, St. Michael’s Hospital, University of Toronto, Ontario, Canada;5. Institute for Global Food Security, School of Biological Sciences, Queen''s University Belfast, Belfast BT9 5DL, United Kingdom;6. Pharmacology, School of Pharmacy Institute for Drug Research, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 9112002, Israel;1. Department of Chemistry and Biochemistry, University of California San Diego, La Jolla, CA 92093-0367, USA;2. UCSD Moores Cancer Center, University of California San Diego, La Jolla, CA 92093-0367, USA;1. Institut de Génétique Humaine, Univ Montpellier, CNRS, Montpellier, France;2. Aarhus University, Department of Biomedicine, Aarhus, Denmark;1. Institute of Medical Immunology, Affiliated Hospital of Jiangsu University, Zhenjiang, China;2. Department of Laboratory Medicine, Affiliated Hospital of Jiangsu University, Zhenjiang, China;3. Department of Rheumatology, the Second People''s Hospital, China Three Gorges University, Yichang, China;4. Department of Rheumatology and immunology, Xiangya Hospital, Central South University, Changsha, China;5. Department of Pathology and Shenzhen Institute of Research and Innovation, The University of Hong Kong; Chongqing International Institute for Immunology, China;6. Department of Gastrointestinal Surgery, Affiliated Hospital of Jiangsu University, Zhenjiang, China;7. Department of Immunology, Jiangsu Key Laboratory of Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, China;1. Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China;2. Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China;3. Shanghai Pancreatic Cancer Institute, Shanghai, China;4. Pancreatic Cancer Institute, Fudan University, Shanghai, China;1. Kinase Biology Laboratory, Barts Cancer Institute, Queen Mary University of London, John Vane Science Centre, Charterhouse Square, London EC1M 6BQ, UK;2. Protein Phosphorylation Laboratory, Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK;3. Transgenic Services, Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK;4. Barts Cancer Institute, Queen Mary, University of London, John Vane Science Centre, Charterhouse Square, London EC1M 6BQ, UK;5. Barts and the London HPB Centre, The Royal London Hospital, Barts Health NHS Trust, Whitechapel, London E1 1BB, UK;6. Unitat de Biofísica i Bioenginyeria, Facultat de Medicina i Ciències de la Salut, Universitat de Barcelona, Barcelona, Spain |
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| Abstract: | Cancer-associated fibroblasts (CAFs), the key component in pancreatic tumor microenvironment (TME), originate from many sources and are naturally heterogeneous in phenotype and function. Numerous studies have identified their crucial role in promoting tumorigenesis through many routes including fostering cancer proliferation, angiogenesis, invasion, and metastasis. Conversely, research also indicates that subsets of CAFs express anti-tumor activity. These dual effects reflect the complexity of CAF heterogeneity and their interactions with other cells and factors in pancreatic TME. A critical component in this environment is infiltrated immune cells and immune mediators, which can communicate with CAFs. The crosstalk occurs via the production of various cytokines, chemokines, and other mediators and shapes the immunological state in TME. Comprehensive studies of the crosstalk between CAFs and tumor immune environment, particularly internal mechanisms interlinking CAFs and immune effectors, may provide new approaches for pancreatic ductal adenocarcinoma (PDAC) treatments. In this review, we explore the characteristics of CAFs, describe the interplay among CAFs, infiltrated immune cells, other mediators, and provide an overview of recent CAF-target therapies, their limitations, and potential research directions in CAF in the context of PDAC. |
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| Keywords: | Cancer-associated fibroblast Immune cells Pancreatic tumor microenvironment CAF-targeted therapy Pancreatic ductal adenocarcinoma (PDAC) |
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