REVIEW article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1555036
This article is part of the Research TopicRoles of Macrophages and Monocytes in Resistance to Immunotherapy in CancersView all 3 articles
Targeting Myeloid Cells in Pancreatic Ductal Adenocarcinoma: From Primary Tumors to Liver Metastasis
Provisionally accepted
- 1The Affiliated Hospital of Qingdao University, Qingdao, China
- 2The Chinese University of Hong Kong, Shatin, Hong Kong Region, China
- 3Hong Kong Polytechnic University, Kowloon, Hong Kong, SAR China
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Pancreatic ductal adenocarcinoma (PDAC) remains one of the malignancies with the highest mortality rates, and outcomes are particularly poor in cases of liver metastasis. Early or recurrent metastatic PDAC significantly worsens patient outcomes and presents substantial clinical challenges. Checkpoint-based immunotherapy has largely been ineffective for most pancreatic cancer patients. This ineffectiveness is not well understood, as clinical trials often involve patients with advanced diseases, such as liver and peritoneal metastases, while most preclinical studies focus on primary tumors. Recent findings indicate that the immunosuppressive tumor microenvironment (TME) is a major obstacle to effective immunotherapy in PDAC, with the metastatic immune microenvironment differing significantly from that of primary tumors. This review explores the distinct immunosuppressive mechanisms at various stages of PDAC progression, including primary tumors, pre-metastatic niches, and metastatic sites. Myeloid cells, such as tumor-associated macrophages (TAMs) and myeloid-derived suppressor cells (MDSCs), play pivotal roles in shaping the TME and suppressing anti-tumor immunity. Particular focus is placed on current clinical immunotherapy strategies targeting myeloid cells, and combinations with conventional chemoradiotherapy, considering contemporary knowledge and future trends. Advancements in single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics have provided deeper insights into the molecular intricacies and diversity of PDAC, revealing potential therapeutic targets. Innovative strategies targeting myeloid cells, including CD40 agonists and CSF-1R inhibitors, are being explored to reprogram the TME and enhance the efficacy of immunotherapies.
Keywords: Pancreatic Cancer, Immunotherapy, macrophage, monocyte, liver metastases
Received: 03 Jan 2025; Accepted: 28 Apr 2025.
Copyright: © 2025 Gong, Chen, Li, Zhang, Liu and Yu. 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 Yu, The Affiliated Hospital of Qingdao University, Qingdao, China
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