Immune cell metabolic reprogramming in pancreatic cancer: roles in tumor progression and therapeutic strategies
4 affiliations
- 1Department of Hepatobiliary and Pancreatic Surgery, Huzhou University Affiliated Central Hospital
- 2Department of Hepatobiliary and Pancreatic Surgery, Huzhou Hospital Affiliated to Zhejiang University
- 3Department of Hepatobiliary and Pancreatic Surgery, Huzhou Central Hospital, Fifth School of Clinical Medicine of Zhejiang Chinese Medical University
- 4Department of Hepatobiliary and Pancreatic Surgery, Lishui Central Hospital
Abstract
Pancreatic cancer is one of the most lethal malignancies of the digestive system, and its profoundly immunosuppressive tumor microenvironment (TME) represents a major driver of tumor progression and therapeutic resistance. Emerging evidence indicates that metabolic reprogramming profoundly influences the polarization, effector function, survival, and fate of immune cells within the TME, thereby shaping the balance between antitumor immunity and immune escape. However, substantial challenges remain, including the incompletely understood metabolic heterogeneity among distinct immune cell subsets and the limited clinical translation of therapeutic strategies combining metabolic intervention with immunotherapy. In this review, we summarize the metabolic reprogramming characteristics and underlying molecular mechanisms of major immune cell populations in pancreatic cancer, including T cells, tumor-associated macrophages (TAMs), myeloid-derived suppressor cells (MDSCs), and natural killer (NK) cells, with particular emphasis on their reciprocal interactions with pancreatic cancer progression and the immunosuppressive microenvironment. We further discuss recent advances in metabolism-targeted therapies and immunotherapy, highlighting the therapeutic potential of combination strategies centered on immunometabolic modulation. Finally, we outline current challenges and emerging opportunities in this rapidly evolving field, with the aim of providing a mechanistic framework and translational perspectives for the development of precision therapeutic strategies for pancreatic cancer.
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BibTeX
@article{gu2026immune,
title = {{Immune cell metabolic reprogramming in pancreatic cancer: roles in tumor progression and therapeutic strategies}},
author = {Gangzhao Gu and Yang Du and Hengzhi Zhang and Yu Zheng and Yanjun Yao and Qiang Yan},
journal = {Frontiers in Immunology},
year = {2026},
month = oct,
doi = {10.3389/fimmu.2026.1968254},
url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1968254/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Immune cell metabolic reprogramming in pancreatic cancer: roles in tumor progression and therapeutic strategies
AU - Gangzhao Gu
AU - Yang Du
AU - Hengzhi Zhang
AU - Yu Zheng
AU - Yanjun Yao
AU - Qiang Yan
PY - 2026
DA - 2026/10/29
JO - Frontiers in Immunology
DO - 10.3389/fimmu.2026.1968254
UR - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1968254/full
AB - Pancreatic cancer is one of the most lethal malignancies of the digestive system, and its profoundly immunosuppressive tumor microenvironment (TME) represents a major driver of tumor progression and therapeutic resistance. Emerging evidence indicates that metabolic reprogramming profoundly influences the polarization, effector function, survival, and fate of immune cells within the TME, thereby shaping the balance between antitumor immunity and immune escape. However, substantial challenges remain, including the incompletely understood metabolic heterogeneity among distinct immune cell subsets and the limited clinical translation of therapeutic strategies combining metabolic intervention with immunotherapy. In this review, we summarize the metabolic reprogramming characteristics and underlying molecular mechanisms of major immune cell populations in pancreatic cancer, including T cells, tumor-associated macrophages (TAMs), myeloid-derived suppressor cells (MDSCs), and natural killer (NK) cells, with particular emphasis on their reciprocal interactions with pancreatic cancer progression and the immunosuppressive microenvironment. We further discuss recent advances in metabolism-targeted therapies and immunotherapy, highlighting the therapeutic potential of combination strategies centered on immunometabolic modulation. Finally, we outline current challenges and emerging opportunities in this rapidly evolving field, with the aim of providing a mechanistic framework and translational perspectives for the development of precision therapeutic strategies for pancreatic cancer.
SN - 1664-3224
ER -