Targeting multidimensional nociceptor-tumor interactions to mitigate immune evasion of cancer
Abstract
Sensory neurons were traditionally viewed as passive detectors of noxious stimuli and mediators of cancer-associated pain. However, accumulating evidence has identified nociceptive sensory neurons as active regulators of tumor biology and immunity in solid tumors. In this review, we summarize recent advances in cancer neuroscience, detailing how tumor-infiltrating nociceptive neurons undergo functional reprogramming to actively participate in tumorigenesis. We first discuss local intratumoral crosstalk, highlighting the direct regulation of immune cells by nociceptive neurons and their indirect immunomodulatory effects through tumor cells and stromal components. We then examine emerging evidence that nociceptive signaling extends beyond the primary tumor through cross-organ neuroimmune communication, particularly via tumor-draining lymph nodes, thereby contributing to systemic immune suppression. Finally, we highlight conventional pharmacological approaches and selective delivery-based strategies aimed at disrupting this neuroimmune axis. Together, this review clarifies the local and systemic roles of nociceptive sensory neurons in tumor immune regulation and discusses their potential as therapeutic targets in cancer.
Authors 15
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Shanghai Institute of Materia Medica
Affiliation as printed
Department of Gastroenterology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200092, China; State Key Laboratory of Chemical Biology & Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China
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Shanghai Institute of Materia Medica
Affiliation as printed
State Key Laboratory of Chemical Biology & Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China; Department of Gastroenterology, Huadong Hospital, Fudan University, Shanghai 200040, China
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Chinese Academy of Sciences · Shanghai Institute of Materia Medica · University of Chinese Academy of Sciences
Affiliation as printed
State Key Laboratory of Chemical Biology & Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China; University of Chinese Academy of Sciences, Beijing 100049, China
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Chinese Academy of Sciences · Shanghai Institute of Materia Medica
Affiliation as printed
State Key Laboratory of Chemical Biology & Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China
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Second Military Medical University · Changhai Hospital
Affiliation as printed
Department of Hepatobiliary Pancreatic Surgery, Changhai Hospital, Naval Medical University (Second Military Medical University), Shanghai 200433, China
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Fudan University · Zhongshan Hospital
Affiliation as printed
Department of Oral and Maxillofacial Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, China
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Chinese Academy of Sciences · Shanghai Institute of Materia Medica
Affiliation as printed
State Key Laboratory of Chemical Biology & Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China
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Affiliation as printed
Department of Pharmaceutics, Ghent University, Ghent 9000, Belgium
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Universitätsklinikum Aachen · RWTH Aachen University
Affiliation as printed
Institute for Experimental Molecular Imaging, RWTH Aachen University Clinic Center for Biohybrid Medical Systems, Aachen 52074, Germany
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University of Chinese Academy of Sciences
Affiliation as printed
University of Chinese Academy of Sciences, Beijing 100049, China
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Second Military Medical University · Changhai Hospital
Affiliation as printed
Department of Hepatobiliary Pancreatic Surgery, Changhai Hospital, Naval Medical University (Second Military Medical University), Shanghai 200433, China
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Zhiai Xu corresponding
Affiliation as printed
School of Chemistry and Molecular Engineering, East China Normal University, Shanghai 200062, China
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徐雷鸣 corresponding
Affiliation as printed
Department of Gastroenterology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200092, China. Electronic address: xuleiming@xinhuamed.com.cn
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Yi Lai corresponding
Chinese Academy of Sciences · Shanghai Institute of Materia Medica
Affiliation as printed
State Key Laboratory of Chemical Biology & Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China. Electronic address: laiyi@simm.ac.cn
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Haijun Yu corresponding
Chinese Academy of Sciences · Shanghai Institute of Materia Medica · University of Chinese Academy of Sciences
Affiliation as printed
State Key Laboratory of Chemical Biology & Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China; University of Chinese Academy of Sciences, Beijing 100049, China. Electronic address: hjyu@simm.ac.cn
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