ReviewFrontiers in immunology2025
The role of the nervous system in the occurrence, development, and immune response of renal cell carcinoma.
Review in Frontiers in immunology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
2 citing papers in PubMed.
- Cancer Neuroscience: From Local Neuro-Immune Microenvironments to Systemic Brain-Body Circuitry.MedComm · 2026Review
- RNA-binding protein RBM47 in health and disease: molecular mechanisms, preclinical evidence, and translational challenges.Frontiers in immunology · 2026Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Renal cell carcinoma (RCC) represents one of the fastest-growing urological malignancies globally, with approximately 30% of patients presenting with metastatic disease at diagnosis. Despite advances in targeted therapy and immune checkpoint inhibitors, treatment resistance remains a critical challenge, largely attributed to the heterogeneous tumor microenvironment (TME). This review systematically examines the emerging role of the neuroimmune system in RCC pathogenesis and progression. The kidney receives dual innervation from sympathetic and parasympathetic systems, which undergo pathological remodeling during tumorigenesis. Novel findings from RCC preclinical models reveal that MANF protein drives sunitinib resistance via IRE1α-XBP1 pathway inhibition, while NPTX2 aberrantly activates PI3K-Akt survival signaling in clear cell renal cell carcinoma (ccRCC). Therapeutic strategies targeting the neuroimmune axis show promise, including β-blockers combined with PD-1 inhibitors to reverse T cell exhaustion, CXCR4 antagonists disrupting nerve- tumor-associated macrophage (TAM) crosstalk, and radiofrequency ablation of perirenal nerve plexus. Future directions involve spatial transcriptomics mapping of the neuroimmune landscape, developing neurotransmitter-targeted delivery systems, and optimizing sequential combination therapies. Understanding the tripartite interaction between nerves, immune cells, and tumor cells opens new avenues for precision medicine in RCC, potentially establishing neuroimmune modulation as a potential new direction of RCC therapy distinct from anti-angiogenesis and immunotherapy.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.