REVIEW article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1619946
This article is part of the Research TopicUnderstanding the Interplay Between Tumor Immune Microenvironment and Neoantigens for Improved ImmunotherapyView all 5 articles
Radiotherapy and Immune Microenvironment Crosstalk in Pancreatic Cancer: A Comprehensive Review of Current Insights and Future Directions
Provisionally accepted
- Nanjing Drum Tower Hospital, Nanjing, China
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Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal malignancies, largely due to its profoundly immunosuppressive tumor microenvironment (TME) and intrinsic resistance to conventional therapies. Radiotherapy (RT), traditionally valued for its cytotoxic effects, has recently been recognized for its immunomodulatory potential. This mini-review explores the multifaceted interactions between RT and the PDAC immune microenvironment, highlighting mechanisms such as induction of immunogenic cell death, enhancement of antigen presentation, modulation of cytokine and chemokine profiles, and upregulation of immune checkpoint molecules. These effects may transform immunologically "cold" tumors into "hot" ones, providing a rationale for combination strategies with immunotherapy. However, the dense desmoplastic stroma, abundance of regulatory T cells, and myeloid-derived suppressor cells within PDAC present substantial challenges that hinder effective immune activation. Advances in single-cell and spatial transcriptomic technologies offer new opportunities to better characterize the TME and guide personalized treatment strategies. By synthesizing mechanistic insights and clinical evidence, this review underscores the potential of integrating RT with immunotherapy to overcome resistance mechanisms and improve therapeutic outcomes in PDAC.
Keywords: Pancreatic ductal adenocarcinoma (PDAC), Tumor microenvironment (TME), Radiotherapy (RT), Immunotherapy, Immune Modulation
Received: 29 Apr 2025; Accepted: 14 Jun 2025.
Copyright: © 2025 Xu, Chen, Qiu and Du. 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: Juan Du, Nanjing Drum Tower Hospital, Nanjing, China
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