Nerve density in cancer: Less is better

Schmitd, Ligia B.; Perez-Pacheco, Cindy; D’Silva, Nisha J.

doi:10.1096/fba.2021-00046

Cited by 17 publications

(18 citation statements)

References 62 publications

(243 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Requires further standardization H&E IHC: Pan-cytokeratin for epithelium, S100 or TUJ1 for nerve. [49,79] H&E: hematoxylin and eosin. IHC: immunohistochemistry phenotypes that have been associated with adverse outcomes, it is time to develop a comprehensive set of neural parameters that can be used to facilitate treatment selection and predict response to treatment of oral cancer.…”

Section: Discussionmentioning

confidence: 99%

“…Nerve fibers are quantified to determine nerve density due to axonogenesis and neurogenesis whereas nerve trunks or fascicles are quantified to assess nerve density due to neurotropism. [79] Factors secreted by nerves, including neurotransmitters, chemokines, neuropeptides, and neurotrophins, enhance neurite growth and cancer progression. In OSCC, the neuropeptide galanin enhances neurite outgrowth as well as growth, invasion, and metastasis of cancer cells.…”

Section: Nerve Densitymentioning

confidence: 99%

See 1 more Smart Citation

The 3D's of Neural Phenotypes in Oral Cancer: Distance, Diameter, and Density

2022

View full text Add to dashboard Cite

She specializes in Oral Medicine and conducted her Ph.D. in the Oral Health Sciences Program at the University of Michigan School of Dentistry. Her Ph.D. work focused on cancer neuroscience, the investigation of nerve-tumor interactions, specifically in oral cavity cancer. She is currently a postdoctoral fellow at the University of Michigan Medical School studying Schwann cell biology in peripheral nervous system injury and regeneration.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Nerve Densitymentioning

confidence: 99%

The 3D's of Neural Phenotypes in Oral Cancer: Distance, Diameter, and Density

2022

View full text Add to dashboard Cite

show abstract

“…[25] In solid tumors, studies from tumors that are developed from highly innervated organs such as pancreatic, head and neck, prostate, and colorectal cancer have shown that nerve density and neurotropism are associated with increased metastasis, morbidity, and mortality. [26][27][28][29] These findings of the impact of nerve density in patient's outcome have led to study different mechanisms of interaction among nerve fibers, tumor cells, and TME.…”

Section: Historical Backgroundmentioning

confidence: 99%

“…[1,76] The implications of the interactions among immune cells and nerve fibers are highlighted by the fact that tumor-associated nerve fiber density is associated to patient's prognosis in several solid tumors. [29] Immune cell and nerve fiber interaction drives physiological processes related to tissue protection, this phenomenon is a key factor for immune-regulation, and has being explained by the presence of functional interrelated paths between the NS and the immune system known as "neuroimmune cell units" (NICUs). In NICUs, immune cells and neuronal cells can colocalize and interact in many tissues around the body playing a significant role in many physiological processes such as tissue repair, inflammation, cancer progression, and especially in immune modulation of T-cells, macrophages, natural killers, and dendritic cells, among others.…”

Section: Interaction Between Nerves and Immune Cellsmentioning

confidence: 99%

The Role of Nerve Fibers in the Tumor Immune Microenvironment of Solid Tumors

2022

View full text Add to dashboard Cite

The concept of solid tumors innervation and tumor associated nerves is a recently emerging area of cancer research, with several studies showing strong evidence of its critical role in tumor biology. [3] Numerous studies in the field of cancer research and neuroscience have identified nerves as key promoters of different pathways of tumor growth and dissemination. In addition, it has been shown that nerves play immune regulatory functions and constitute an essential component of cellular microenvironments. [4] Furthermore, nerves seem to modulate many signaling pathways in tumor cells and other cellular elements of the TME. [5] The assessment of the presence, type, and density of nerve fibers performed in tumor tissue offers several opportunities to study nerve-related mechanisms implicated in tumor development. This is supported by studies revealing that differences of nerve fiber density in tumors, such as in pancreatic carcinoma, correlated patient's prognosis. [6] There are many techniques that can be used to evaluate nerve fibers in tissue, namely, routine hematoxylin and eosin (H&E) staining combined with micro scopy evaluation and more advanced technologies including artificial intelligence or hi-plex techniques that allow the analysis of several biomarkers in limited tissue samples. [7,8] More importantly, understanding the mutual interactions between nerves and solid tumors may accelerate the development of novel drugs and surgical therapeutic approaches. [9] Nerves seem to have a trophic and immune impact in tumors similarly to the well-known nerve functions in tissue regeneration, and in immunity, these features can potentially be exploited to develop novel and more efficacious therapeutic approaches. [10,11] These new therapeutic targets, alone or in combination with chemotherapy or immunotherapy could slow or stop cancer progression. [12] In this review we will briefly describe the historical background of the study of nerves in tumors, the mechanisms associated with this emergent concept of nerve fibers as important players in the TME including innervation of solid tumors, mechanisms of nerve fiber neogenesis, the complex interactions among nerve fibers and TME elements including immune cells, and its impact in tumor initiation and disease progression; we will also provide a summary of the approaches that can be used to assess tumor associated nerves in tissue;The importance of neurons and nerve fibers in the tumor microenvironment (TME) of solid tumors is now acknowledged after being unexplored for a long time; this is possible due to the development of new technologies that allow in situ characterization of the TME. Recent studies have shown that the density and types of nerves that innervate tumors can predict a patient's clinical outcome and drive several processes of tumor biology. Nowadays, several efforts in cancer research and neuroscience are taking place to elucidate the mechanisms that drive tumor-associated innervation and nerve-tumor and nerve-immune interaction. Assessment of neurons a...

show abstract

“…Determining the outcome of the tumor at the time of diagnosis is increasingly important for treatment choice and patient segmentation, and as nerve infiltration in the tumor microenvironment is associated with tumor aggressiveness 31,58,59,76 , the assessment of nerve density may become part of routine clinicopathological analyses in oncology, as well as increasing utility through imaging, particularly in prostate cancer 77 . Similarly, neurotrophic growth factors and their receptors are overexpressed in human tumors 78,79,80,81 and they could also be of value in cancer clinicopathology.…”

Section: -Conclusion: Emerging Clinical Translationmentioning

confidence: 99%

The nervous system: Orchestra conductor in cancer, regeneration, inflammation and immunity

2021

View full text Add to dashboard Cite

Although the role of nerves in stimulating cellular growth and dissemination has long been described in tissue regeneration studies, until recently a similar trophic role of nerves in disease was not well-recognized. However, recent studies in oncology have demonstrated that the growth and dissemination of cancers also requires the infiltration of nerves in the tumor microenvironment. Nerves generate various neuro-signaling pathways, which orchestrate cancer initiation, progression and metastases. Similarly, nerves are increasingly implicated for their regulatory functions in immunity and inflammation. This orchestrator role of nerves in cellular and molecular interactions during regeneration, cancer, immunity and inflammation offers new possibilities for targeting or enhancing neuro-signaling in human health and diseases.

show abstract

Nerve density in cancer: Less is better

Cited by 17 publications

References 62 publications

The 3D's of Neural Phenotypes in Oral Cancer: Distance, Diameter, and Density

The 3D's of Neural Phenotypes in Oral Cancer: Distance, Diameter, and Density

The Role of Nerve Fibers in the Tumor Immune Microenvironment of Solid Tumors

The nervous system: Orchestra conductor in cancer, regeneration, inflammation and immunity

Contact Info

Product

Resources

About