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Neuroimmunometabolic co-evolution in the tumor micro- and macroenvironment
Yu Zhang1, Weijie Zhuang2, Haodong Zhu3
1Department of Oral and Maxillofacial Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, China; Department of Hepatobiliary Surgery and Liver Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai 200032, China; Department of Stomatology, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
Cell Metabolism
|February 28, 2026
Summary
The nervous system intricately links with immune and metabolic systems to influence cancer progression and treatment. Understanding these neuroimmunometabolic interactions in the tumor microenvironment and macroenvironment is key for developing new therapies.
Area of Science:
- Neuroscience
- Immunology
- Metabolism
- Oncology
Background:
- The nervous system integrates immune, endocrine, and circulatory functions for physiological coordination.
- The nervous system significantly impacts tumor progression and treatment resistance.
- Interactions occur at both the tumor microenvironment (TME) and tumor macroenvironment (TMaE) levels.
Purpose of the Study:
- To provide a comprehensive review of neuroimmunometabolic co-evolution within the TME and TMaE.
- To elucidate the role of the peripheral nervous system (PNS) in regulating metabolic and immune functions within the TME.
- To highlight how cancer exploits brain-body interactions to alter systemic metabolism and immunity in the TMaE.
Main Methods:
- Literature review focusing on neuroimmunometabolic interactions in cancer.
- Analysis of the peripheral nervous system's (PNS) role at the TME scale.
- Examination of brain-body communication and its impact on systemic metabolism and immunity at the TMaE scale.
Main Results:
- The PNS, comprising sympathetic, parasympathetic, and sensory neurons, modulates metabolic processes and immune cell functions within the TME.
- Cancer cells leverage brain-body interactions to reprogram systemic metabolism and immune responses, fostering tumor growth.
- The PNS acts as a critical communication pathway between tumors and distant organs.
Conclusions:
- Neuroimmunometabolic interactions are central to cancer progression and therapeutic resistance.
- Targeting neuroimmune and neurometabolic pathways offers potential for novel cancer therapies.
- Further research is needed to address knowledge gaps in neuroimmunometabolism for clinical application.
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