bims-netuvo 2025-04-27 papers

Med Oncol. 2025 Apr 22. 42(5): 171

Molecular mechanisms and clinical significance of perineural invasion in malignancies: the pivotal role of tumor-associated Schwann cells in cancer progression and metastasis.

Noura A A Ebrahim, Soliman M A Soliman, Moamen O Othman, Neveen S Tahoun.

Perineural invasion (PNI) is a pathological process wherein cancer cells invade and spread along peripheral nerves, contributing to tumor aggressiveness and poor clinical outcomes, including increased recurrence, metastasis, and reduced survival. Tumor-associated Schwann cells (SCs) play a pivotal role in facilitating PNI by promoting epithelial-mesenchymal transition (EMT), extracellular matrix (ECM) remodeling, and immune modulation. These cells actively support tumor progression through neurotrophin, cytokine, chemokine, and neurotransmitter signaling, enhancing cancer cell migration along neural pathways. Recent advances in imaging techniques, single-cell transcriptomics, and molecular profiling have provided deeper insights into the tumor microenvironment's role in PNI. Emerging therapeutic strategies targeting neurotrophin-mediated signaling and SC-tumor interactions have shown promise in preclinical models. However, significant research gaps remain, particularly in understanding the heterogeneity of SCs and their molecular subtypes in PNI across different malignancies. This review highlights the clinical significance, molecular mechanisms, and potential therapeutic targets associated with PNI. A comprehensive understanding of tumor-SC interactions is essential for developing targeted interventions to mitigate PNI-driven malignancies. Future research should focus on integrating multi-omics approaches and novel therapeutics to improve early detection and treatment, ultimately enhancing patient outcomes.

Keywords: Metastasis; Neurotrophins; Perineural invasion; Schwann cells; Tumor progression

DOI: https://doi.org/10.1007/s12032-025-02729-x

iScience. 2025 May 16. 28(5): 112321

Sleep deprivation-induced sympathetic activation promotes pro-tumoral macrophage phenotype via the ADRB2/KLF4 pathway to facilitate NSCLC metastasis.

Shuxian Yin, Jiali Wang, Yunlong Jia, Xiaoyi Wang, Yan Zhao, Tianxu Liu, Wei Lv, Yuqing Duan, Song Zhao, Sheng Wang, Lihua Liu.

Sleep deprivation is one of concomitant symptoms of cancer patients, particularly those with non-small cell lung cancer (NSCLC). The potential effect of sleep deprivation on tumor progression and underlying mechanisms remain to be fully investigated. Using a sleep-deprived tumor-bearing mouse model, we found that sleep deprivation altered immune cell composition and regulated pro-tumoral M2 macrophage polarization by the sympathetic nervous system. Furthermore, we identified a role of catecholaminergic neurons in the rostral ventrolateral medulla (RVLM) in influencing NSCLC metastasis. Clinical analyses revealed a correlation between sympathetic-related indicators and poor prognosis. Mechanistically, our findings indicate that sleep deprivation facilitates the polarization of pro-tumoral macrophages by upregulating β2-adrenergic receptor (ADRB2), which subsequently enhances the expression of Kruppel-like transcription factor 4 (KLF4) through the JAK1/STAT6 phosphorylation pathway. These findings highlight a neuro-immune mechanism linking sleep deprivation to NSCLC metastasis, suggesting that targeting the ADRB2/KLF4 axis could improve outcomes for sleep-deprived NSCLC patients.

Keywords: Biological sciences; Cancer systems biology; Microenvironment; Natural sciences; Physiology; Systems biology

DOI: https://doi.org/10.1016/j.isci.2025.112321

Cytokine Growth Factor Rev. 2025 Apr 19. pii: S1359-6101(25)00044-9. [Epub ahead of print]

Decoding the neuroimmune axis in colorectal cancer: From neural circuitry to therapeutic innovation.

Ying Li, Sheng-Ya Yang, Ying-Ru Zhang, Yan Wang.

The nervous and immune systems are two major components that maintain body homeostasis, with their functional roles often overlapping significantly. Both systems are capable of identifying, integrating, and organizing responsive reactions to various external stimuli. The gut, referred to as the "second brain" and the largest immune organ in the body, serves as the most frequent focal site for neuroimmune interactions. Colorectal cancer (CRC), as the predominant solid tumor arising in this neuroimmune-rich microenvironment, remains understudied through the lens of neuroimmune regulatory mechanisms. This review systematically synthesizes current evidence to elucidate the neuroimmune axis in CRC pathogenesis, with particular emphasis on neuroimmune crosstalk-mediated remodeling of tumor immunity. We comprehensively catalog the immunomodulatory effects exerted by principal neuroregulatory mediators, categorized as: (1) neurotransmitters (glutamate, glutamine, γ-aminobutyric acid, epinephrine, norepinephrine, dopamine, serotonin, acetylcholine, and gaseous signaling molecules); (2) neuropeptides (substance P, calcitonin gene-related peptide, vasoactive intestinal peptide); and (3) neurotrophic factors. Furthermore, we critically evaluate the translational prospects and therapeutic challenges of targeting neuroimmune pathways and propose strategic priorities and research focuses for advancing the development of neuroimmune interaction-related therapeutic approaches in CRC.

Keywords: Colorectal cancer; Enteric nervous system; Gut-brain axis; Neuroimmune Interactions; Neurotransmitter

DOI: https://doi.org/10.1016/j.cytogfr.2025.04.001