REVIEW article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1585858
This article is part of the Research TopicAdvances in Immunosuppressive Microenvironment Remodeling and Targeted Drug Intervention in Pancreatic CancerView all 4 articles
Domestication and Feedback: Bidirectional Hijacking in Pancreatic Ductal Adenocarcinoma Microenvironment
Provisionally accepted
- 1Liaoning Cancer Hospital, China Medical University, Shenyang, Liaoning Province, China
- 2Departments of Pathology, Liaoning Cancer Hospital, China Medical University, Shenyang, Liaoning Province, China
- 3Medical Oncology Department of Gastrointestinal Tumors, Liaoning Cancer Hospital & Institute, Cancer Hospital of Dalian University of Technology, Cancer Hospital of China Medical University, Shenyang, Liaoning Province, China
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Pancreatic ductal adenocarcinoma (PDAC) is characterized by a tumor microenvironment (TME) composed of a dense extracellular matrix, cancer-associated fibroblasts, vasculature, neural elements, and immune cell populations. This complex network promotes tumor proliferation, invasion, metastasis, and resistance to immunotherapy and chemotherapy. The microenvironmental characteristics of the various PDAC subtypes are discussed in this review. And we examines the role of cancer cells in the tumor microenvironment, highlighting their ability to manipulate stromal components to serve as collaborators in tumor progression. Furthermore, we explored the formation mechanism of the immunosuppressive microenvironment in PDAC, paying attention on Inflammation and intrinsic genetic alterations, the regulatory effect of metabolic reprogramming, the contribution of CAFs and the role of immune cells in cancer cell metastasis. This review shows the role of soluble molecules and exosomes in facilitating PDAC progression and immune evasion within the microenvironment. In conclusion, we outline the novel therapeutic strategies that focus on the interaction between cancer cells and their microenvironment, with the objective of offering new insights for future precision medical interventions.
Keywords: Pancreatic Ductal Adenocarcinoma, Tumor Microenvironment, Tumor-associated fibroblasts, combination therapy, Extracellular Matrix
Received: 31 Mar 2025; Accepted: 14 Jul 2025.
Copyright: © 2025 Qiao, Yin, Zhang, Zhang and Dong. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Qian Dong, Medical Oncology Department of Gastrointestinal Tumors, Liaoning Cancer Hospital & Institute, Cancer Hospital of Dalian University of Technology, Cancer Hospital of China Medical University, Shenyang, Liaoning Province, China
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