Schwann Cells in Peripheral Cancers: Bystanders or Promoters?

Yurteri, Ümmügülsüm; Çifcibaşı, Kaan; Friess, Helmut; Ceyhan, Güralp O.; Istvànffy, Rouzanna; Demir, Ihsan Ekin

doi:10.1002/adbi.202200033

Cited by 6 publications

(7 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…SC have been recently shown to play a role in maintenance of the immunosuppressive tumor microenvironment by chemoattraction and polarization of myeloid regulatory cells and upregulating their ability to reduce activity of T cells [ 20 , 22 , 34 ]. SC were also reported to be capable of directly stimulating malignant cell motility and formation of metastases [ 21 , 35 , 36 ]. However, SC-derived factors affecting myeloid regulatory cells have not been yet identified.…”

Section: Discussionmentioning

confidence: 99%

Tumor-Induced T Cell Polarization by Schwann Cells

Shurin

Vats

Kruglov

et al. 2022

Cells

View full text Add to dashboard Cite

Nerve-cancer crosstalk resulting in either tumor neurogenesis or intratumoral neurodegeneration is critically controlled by Schwann cells, the principal glial cells of the peripheral nervous system. Though the direct stimulating effect of Schwann cells on malignant cell proliferation, motility, epithelial–mesenchymal transition, and the formation of metastases have been intensively investigated, the ability of Schwann cells to affect the effector and regulatory immune cells in the tumor environment is significantly less studied. Here, we demonstrated that tumor cells could stimulate Schwann cells to produce high levels of prostaglandin E, which could be blocked by COX-2 inhibitors. This effect was mediated by tumor-derived TGF-β as neutralization of this cytokine in the tumor-conditioned medium completely blocked the inducible prostaglandin E production by Schwann cells. Similar protective effects were also induced by the Schwann cell pretreatment with TGF-βR1/ALK4/5/7 and MAPK/ERK kinase inhibitors of the canonical and non-canonical TGF-β signaling pathways, respectively. Furthermore, prostaglandin E derived from tumor-activated Schwann cells blocked the proliferation of CD3/CD28-activated T cells and upregulated the expression of CD73 and PD-1 on both CD4+ and CD8+ T cells, suggesting T cell polarization to the exhausted phenotype. This new pathway of tumor-induced T cell inhibition via the activation of neuroglial cells represents new evidence of the importance of nerve–cancer crosstalk in controlling tumor development and progression. A better understanding of the tumor-neuro-immune axis supports the development of efficient targets for harnessing this axis and improving the efficacy of cancer therapy.

show abstract

Section: Discussionmentioning

confidence: 99%

Tumor-Induced T Cell Polarization by Schwann Cells

Shurin

Vats

Kruglov

et al. 2022

Cells

View full text Add to dashboard Cite

show abstract

“…Our recognition of the relevance of SC activity and lung cancer is still in its infancy although the important role of SCs in other cancer types has already been demonstrated ( Deborde and Wong, 2017 ; Martyn et al, 2019 ; Shurin et al, 2021 ; Deborde and Wong, 2022 ; Yurteri et al, 2022 ). Analysis of SC biology in prostate, pancreatic, cervical, oral, colon tumors, melanoma, and other cancer types revealed their involvement in perineural invasion, cancer pain, and tumor cell proliferation, dispersion, invasion, and metastasizing ( Demir et al, 2014 ; Deborde et al, 2016 ; Shan et al, 2016 ; Shurin et al, 2019 ; Huang et al, 2020 ; Salvo et al, 2021 ; Santi et al, 2022 ).…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, it was also observed that advanced stages of lung cancer exhibited the highest levels of SC detection ( Zhou et al, 2019 ). Although the identification of SCs in different solid tumors and their role in the development and metastasis formation in different types of cancer have been repeatedly reported and reviewed ( Bunimovich et al, 2017 ; Deborde and Wong, 2022 ; Sun et al, 2022 ; Yurteri et al, 2022 ; Xue et al, 2023 ), data describing the functional significance of tumor-associated SCs (TA-SCs) in lung cancer are scarce ( Table 1 ).…”

Section: Introductionmentioning

confidence: 99%

Schwann cells in the normal and pathological lung microenvironment

Shurin,

Wheeler,

Shurin

et al. 2024

Front. Mol. Biosci.

View full text Add to dashboard Cite

The lungs are a key organ in the respiratory system. They are regulated by a complex network of nerves that control their development, structure, function, and response to various pathological stimuli. Accumulating evidence suggests the involvement of a neural mechanism in different pathophysiological conditions in the lungs and the development and progression of common respiratory diseases. Lung diseases are the chief source of death globally. For instance, lung cancer is the second most commonly diagnosed malignancy, after prostate cancer in men and breast cancer in women, and is the most lethal cancer worldwide. However, although airway nerves are accepted as a mechanistically and therapeutically important feature that demands appropriate emphasizing in the context of many respiratory diseases, significantly less is known about the role of the neuroglial cells in lung physiology and pathophysiology, including lung cancer. New data have uncovered some cellular and molecular mechanisms of how Schwann cells, as fundamental components of the peripheral nervous system, may regulate lung cancer cells’ survival, spreading, and invasiveness in vitro and in vivo. Schwann cells control the formation and maintenance of the lung cancer microenvironment and support metastasis formation. It was also reported that the number of lung cancer-associated Schwann cells correlates with patients’ survival. Different factors secreted by Schwann cells, including microRNA, are known to sharpen the lung cancer environment by regulating the tumor-neuro-immune axis. Further clinical and experimental studies are required to elucidate the detailed role of Schwann cells in creating and maintaining pulmonary tumor-neuro-immune axis, which will advance our understanding of the pathogenesis of lung cancer and may inform therapeutic hypotheses aiming neoplasms and metastases in the lung.

show abstract

“…Such a dynamic communication between the nerves and PDAC cells further facilitates immune escape, tumor growth, and metastasis. SCs are believed to possess the potential to drive tumorigenesis, produce signals to promote cancer invasion, and reshape the ECM [ 40 ]. From a clinical perspective, the development of novel therapies targeting the modification of SCs’ repair phenotype holds promise for mitigating perineural invasion in PDAC.…”

Section: Discussionmentioning

confidence: 99%

Unraveling the Connection: Pancreatic Cancer Cells and Schwann Cells

Garajová,

Trentini,

Leonardi

et al. 2024

JCM

View full text Add to dashboard Cite

Pancreatic ductal adenocarcinoma is one of the most lethal solid malignancies, characterized by its aggressiveness and metastatic potential, with a 5-year survival rate of only 13%. Progress in the management of metastatic disease has been modest. A robust connection between nervous system and tumor progression exists, with prominent neural alterations having been observed during pancreatic cancer’s progression, including neural hypertrophy, neural density, and neural remodeling. The pancreatic tumor microenvironment includes s set of cells and structures that constantly dialogue with cancer cells, influencing its growth and behavior. The microglia is key cellular components of the tumor microenvironment, and Schwann cells are the principal glial cells in the peripheral neural system. Schwann cells can regulate changes in the tumor microenvironment and immune responses by secreting a variety of factors and can support a tumor’s invasion of nerves and distant metastasis, with further pain exacerbation. Schwann cells secrete various pain-related molecules, such as the neural growth factor, to mediate the activation of primary sensory neurons, leading to pain induction. The binding of the neural growth factor to tropomyosin receptor kinase A is an important signaling mechanism for pain perception in humans. Consequently, directing efforts towards targeting neural invasion may provide an alternative strategy to improve the prognosis of and alleviate pain in patients with pancreatic cancer.

show abstract

Schwann Cells in Peripheral Cancers: Bystanders or Promoters?

Abstract: The ORCID identification number(s) for the author(s) of this article can be found under https://doi.org/10.1002/adbi.202200033.

Cited by 6 publications

References 47 publications

Tumor-Induced T Cell Polarization by Schwann Cells

Tumor-Induced T Cell Polarization by Schwann Cells

Schwann cells in the normal and pathological lung microenvironment

Unraveling the Connection: Pancreatic Cancer Cells and Schwann Cells

Contact Info

Product

Resources

About