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Peer-reviewedCC BY 4.0Frontiers in Immunology

The obesity–neuroinflammation–cancer axis: neuroimmune remodeling and therapeutic opportunities

  • Nan Yang1
  • Wei Zhang2
  • Yinsheng Zhong1
  • Zhenghua Ding1
  1. 1Department of General Surgery, Xiangyang No 1 People’s Hospital, Hubei University of Medicine
  2. 2Henan Key Laboratory of Cancer Epigenetics, Cancer Hospital, The First Affiliated Hospital, College of Clinical Medicine, Medical College of Henan University of Science and Technology
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Abstract

Obesity is a chronic metabolic and inflammatory disorder associated with increased risk and poorer outcomes in multiple malignancies. Although adipose inflammation, insulin resistance, and altered adipokine signaling are established links between obesity and cancer, these mechanisms do not fully explain how systemic metabolic stress is translated into persistent changes in tissue immunity and tumor behavior. This narrative Review proposes the obesity–neuroinflammation–cancer axis as an integrative framework in which obesity-associated metabolic and inflammatory signals perturb central and peripheral neural homeostasis, while neuroinflammation, neural remodeling, and neuroendocrine signaling reshape the tumor microenvironment through reciprocal interactions among nerves, immune cells, stromal cells, and cancer cells. We focus on obesity-induced neuroinflammation, tumor neuroimmune remodeling, and neuroimmunometabolic feedback, highlighting sympathetic signaling, leptin–JAK/STAT3, NF-κB, inflammasome pathways, and metabolic reprogramming. We further evaluate therapeutic opportunities involving metabolic, inflammatory, and adrenergic interventions, including their combination with immune checkpoint blockade, while emphasizing inconsistent clinical evidence and the need for composite biomarkers. This framework is intended as a testable synthesis rather than a universally established causal pathway and identifies cancer-type-specific neuroimmune circuits as a priority for future translational research.

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Cite

BibTeXRIS
BibTeX
@article{yang2026obesityneuroinflammationcancer,
  title = {{The obesity–neuroinflammation–cancer axis: neuroimmune remodeling and therapeutic opportunities}},
  author = {Nan Yang and Wei Zhang and Yinsheng Zhong and Zhenghua Ding},
  journal = {Frontiers in Immunology},
  year = {2026},
  month = oct,
  doi = {10.3389/fimmu.2026.1999371},
  url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1999371/full},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - The obesity–neuroinflammation–cancer axis: neuroimmune remodeling and therapeutic opportunities
AU  - Nan Yang
AU  - Wei Zhang
AU  - Yinsheng Zhong
AU  - Zhenghua Ding
PY  - 2026
DA  - 2026/10/26
JO  - Frontiers in Immunology
DO  - 10.3389/fimmu.2026.1999371
UR  - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1999371/full
AB  - Obesity is a chronic metabolic and inflammatory disorder associated with increased risk and poorer outcomes in multiple malignancies. Although adipose inflammation, insulin resistance, and altered adipokine signaling are established links between obesity and cancer, these mechanisms do not fully explain how systemic metabolic stress is translated into persistent changes in tissue immunity and tumor behavior. This narrative Review proposes the obesity–neuroinflammation–cancer axis as an integrative framework in which obesity-associated metabolic and inflammatory signals perturb central and peripheral neural homeostasis, while neuroinflammation, neural remodeling, and neuroendocrine signaling reshape the tumor microenvironment through reciprocal interactions among nerves, immune cells, stromal cells, and cancer cells. We focus on obesity-induced neuroinflammation, tumor neuroimmune remodeling, and neuroimmunometabolic feedback, highlighting sympathetic signaling, leptin–JAK/STAT3, NF-κB, inflammasome pathways, and metabolic reprogramming. We further evaluate therapeutic opportunities involving metabolic, inflammatory, and adrenergic interventions, including their combination with immune checkpoint blockade, while emphasizing inconsistent clinical evidence and the need for composite biomarkers. This framework is intended as a testable synthesis rather than a universally established causal pathway and identifies cancer-type-specific neuroimmune circuits as a priority for future translational research.
SN  - 1664-3224
ER  -