bims-netuvo 2023-11-05 papers

Issue of 2023‒11‒05
six papers selected by
Maksym V. Kopanitsa, The Francis Crick Institute

Cell Oncol (Dordr). 2023 Oct 30.

TRPV1 inhibition suppresses non-small cell lung cancer progression by inhibiting tumour growth and enhancing the immune response.

Yang Wang, Yu Zhang, Jing Ouyang, Hanying Yi, Shiyu Wang, Dongbo Liu, Yingying Dai, Kun Song, Wenwu Pei, Ziyang Hong, Ling Chen, Wei Zhang, Zhaoqian Liu, Howard L Mcleod, Yijing He.

PURPOSE: TRPV1 is a nonselective Ca2+ channel protein that is widely expressed and plays an important role during the occurrence and development of many cancers. Activation of TRPV1 channels can affect tumour progression by regulating proliferation, apoptosis and migration. Some studies have also shown that activating TRPV1 can affect tumour progression by modulating tumour immunity. However, the effects of TRPV1 on the development of non-small cell lung cancer (NSCLC) have not been explored clearly.METHOD: The Cancer Genome Atlas (TCGA) database and spatial transcriptomics datasets from 10 × Genomics were used to analyze TRPV1 expression in various tumour tissues. Cell proliferation and apoptosis were examined by cell counting kit 8 (CCK8), colony formation, and flow cytometry. Immunohistochemistry, qPCR, and western blotting were used to determine the mRNA and protein expression levels of TRPV1 and other related molecules. Tumour xenografts in BALB/C and C57BL/6J mice were used to determine the effects of TRPV1 on NSCLC development in vivo. Neurotransmitter content was examined by LC-MS/MS, ELISA and Immunohistochemistry. Immune cell infiltration was assessed by flow cytometry.
RESULTS: In this study, we found that TRPV1 expression was significantly upregulated in NSCLC and that patients with high TRPV1 expression had a poor prognosis. TRPV1 knockdown can significantly inhibit NSCLC proliferation and induce cell apoptosis through Ca2+-IGF1R signaling. In addition, TRPV1 knockdown resulted in increased infiltration of CD4+ T cells, CD8+ T cells, GZMB+CD8+ T cells and DCs and decreased infiltration of immunosuppressive MDSCs in NSCLC. In addition, TRPV1 knockout effectively decreased the expression of M2 macrophage markers CD163 and increased the expression of M1-associated, costimulatory markers CD86. Knockdown or knockout of TRPV1 significantly inhibit tumour growth and promoted an antitumour immune response through supressing γ-aminobutyric acid (GABA) secretion in NSCLC.
CONCLUSION: Our study suggests that TRPV1 acts as a tumour promoter in NSCLC, mediating pro-proliferative and anti-apoptotic effects on NSCLC through IGF1R signaling and regulating GABA release to affect the tumour immune response.

Keywords: Ca2+ channel; IGF1R; Immune; Non-small cell lung cancer; TRPV1; γ-aminobutyric acid

DOI: https://doi.org/10.1007/s13402-023-00894-7

Biochim Biophys Acta Rev Cancer. 2023 Oct 29. pii: S0304-419X(23)00156-7. [Epub ahead of print] 189007

The association between the neuroendocrine system and the tumor immune microenvironment: Emerging directions for cancer immunotherapy.

Jie Li, Mengjie Che, Bin Zhang, Kewei Zhao, Chao Wan, Kunyu Yang.

This review summarizes emerging evidence that the neuroendocrine system is involved in the regulation of the tumor immune microenvironment (TIME) to influence cancer progression. The basis of the interaction between the neuroendocrine system and cancer is usually achieved by the infiltration of nerve fibers into the tumor tissue, which is called neurogenesis; the migration of cancer cells toward nerve fibers, which is called perineural invasion (PNI), and the neurotransmitters. In addition to the traditional role of neurotransmitters in neural communications, neurotransmitters are increasingly recognized as mediators of crosstalk between the nervous system, cancer cells, and the immune system.Recent studies have revealed that not only nerve fibers but also cancer cells and immune cells within the TIME can secrete neurotransmitters, exerting influence on both neurons and themselves. Furthermore, immune cells infiltrating the tumor environment have been found to express a wide array of neurotransmitter receptors. Hence, targeting these neurotransmitter receptors may promote the activity of immune cells in the tumor microenvironment and exert anti-tumor immunity. Herein, we discuss the crosstalk between the neuroendocrine system and tumor-infiltrating immune cells, which may provide feasible cancer immunotherapy options.

Keywords: Immune cells; Immunotherapy; Nerve fiber; Neurotransmitter; Tumor microenvironment

DOI: https://doi.org/10.1016/j.bbcan.2023.189007

Respirol Case Rep. 2023 Dec;11(12): e01241

Primary benign intratracheal schwannoma: A case report and review of the literature.

Shahab Rafieian, Reza Ershadi, Hesam Amini, Alireza Samimiat, Mohsen Gholinataj Jelodar, Matin Vahedi.

Shwannomas are rare benign tumours especially in tracheal. A 16-year-old male presented with a chronic cough, and a thoracic CT scan revealed a pedunculated tumour measuring approximately 11 × 13 mm in size, located 22 mm away from the main carina. Tissue sample was obtained via rigid bronchoscopy and cryobiopsy, and the pathological analysis confirmed the diagnosis of a benign nerve sheath tumour consistent with schwannoma. The patient subsequently underwent resection of the tumour and tracheal anastomosis. Schwannomas are uncommon pulmonary tumours that typically occur in adults, with a higher incidence among females. The presenting symptoms vary depending on the size and location of the tumour. Treatment options include therapeutic bronchoscopy or surgical resection, with the choice of approach based on tumour characteristics (pedunculated or sessile), preoperative surgical risk, and risk of recurrence. The prognosis is generally favourable, with a low risk of recurrence and excellent outcomes.

Keywords: resection; schwannoma; trachea

DOI: https://doi.org/10.1002/rcr2.1241

Skeletal Radiol. 2023 Oct 31.

Association of plexiform and diffuse neurofibromas with malignant peripheral nerve sheath tumor in NF I patients: a whole-body MRI assessment.

Sarah Attia, Mina Guirguis, Lu Q Le, Avneesh Chhabra.

OBJECTIVE: The aim of this study is to evaluate neurofibromatosis type 1 (NF1) patients with whole-body MRI (WBMRI) to investigate the frequency of plexiform neurofibromas (pNFs), diffuse neurofibromas (dNFs), and malignant peripheral nerve sheath tumors (MPNSTs).MATERIALS AND METHODS: In this retrospective cross-sectional study, between the years 2015 and 2023, 83 consecutive patients with known NF1 underwent a total of 110 WBMRI screenings for MPNST using a standardized institutional protocol. The lesions are categorized as discrete lesions, pNFs, dNFs, and MPNSTs. Histopathology served as the reference standard for all MPNSTs.
RESULTS: Among the 83 patients analyzed, 53 (64%) were women and 30 were men (36%) of ages 36.94±14.43 years (range, 15-66 years). Of the 83 patients, 33 have a positive family history of NF1 and positive genetic studies. Seven of 83 (8%) have only dNF, 20/83 (24%) have pNF, 28/83 (34%) have both dNF and pNF, and 28/83 (34%) have neither. Of the 83 patients, eight (9.6%) were diagnosed with nine total MPNSTs. Age range for patients with MPNSTs at time of diagnosis was 22-51, with an average age of 33.4 years. Only one MPNST (11%) developed from underlying pNF 4 years after WBMRI along the right bronchial tree. Three of eight (37.5%) patients with MPNST died within 5 years of pathologic diagnosis.
CONCLUSION: This study suggests the absence of a predisposition for development of MPNST from pNFs and dNFs in the setting of NF1. As such, these lesions may not need special surveillance compared to discrete peripheral nerve sheath tumors.

Keywords: Diffuse neurofibroma; Malignant peripheral nerve sheath tumor; Neurofibromatosis; Plexiform neurofibroma; Whole-body MRI

DOI: https://doi.org/10.1007/s00256-023-04497-z

Curr Oncol Rep. 2023 Oct 31.

Management of Central and Peripheral Nervous System Tumors in Patients with Neurofibromatosis.

Rebecca Brown.

Neurofibromatosis type I (NF1), neurofibromatosis type 2 (NF2), and schwannomatosis represent a diverse group of genetic tumor predisposition syndromes with a shared feature of tumors affecting the peripheral nerve sheaths. PURPOSE OF REVIEW: Many advancements have been made in understanding the biologic underpinnings of these conditions, and in 2016 the first drug was approved by the FDA to treat pediatric symptomatic unresectable plexiform neurofibromas. RECENT FINDINGS: Mek inhibitors have provided a much-needed therapeutic avenue for NF1 patients with unresectable plexiform neurofibromas (PN), both for reduction of tumor bulk and for improvement in symptoms. Selumetinib is the first FDA approved drug for PN, but is only approved for children. Some research suggests that alternative Mek inhibitors and other mixed tyrosine kinase inhibitors may have better efficacy in adults. Vascular endothelial growth factor (VEGF) inhibitor bevacizumab can prolong hearing and delay the need for surgery in NF2 patients with bilateral vestibular schwannomas. This article provides an update regarding considerations and approaches when treating the tumors associated with the neurofibromatoses (NF), including risk and prognosis metrics, clinical trial results, surgical techniques, and radiation therapy recommendations.

Keywords: ANNUBP; Atypical Neurofibromatous Neoplasm of Uncertain Biologic Potential; Cutaneous neurofibroma; Distinct Nodular Lesion NF1; MPNST; Malignant peripheral nerve sheath tumor; Meningioma; NF2; Neurofibromatosis; Plexiform neurofibroma; Schwannomatosis; Selumetinib; Vestibular Schwannoma

DOI: https://doi.org/10.1007/s11912-023-01451-z

Case Rep Oncol. 2023 Jan-Dec;16(1):16(1): 1142-1147

Localized Multifocal Retroperitoneal Ganglioneuroma with an Infiltrative Appearance on Imaging: A Case Report.

Joseph M Rich, Vinay A Duddalwar, Manju Aron, Ramon Ter-Oganesyan, Peter Hu, Shefali Chopra, Phillip M Cheng.

Multifocal ganglioneuromas are characterized by the presence of multiple benign neuroepithelial tumor nodules and are less common than solitary tumors. A small percentage of ganglioneuromas present with a fatty appearance. Only a few cases of multifocal ganglioneuromas have been reported, due to both their rarity and minimal symptomatic presentation; therefore, generalizations about risk factors and predictive markers are very difficult. Here, we report a case of multifocal retroperitoneal ganglioneuroma with an infiltrative appearance on computed tomography (CT). The tumor demonstrated slow growth on multiple imaging studies and was associated with abdominal and flank pain. The aggressive appearance eventually led to surgical resection 18 months after the initial incidental finding on CT. Postsurgical analysis of the tumor on imaging was crucial in revealing its nodularity and infiltration, as well as for clarifying its retroperitoneal location inseparable from the adrenal gland. Histology demonstrated Schwann cells and ganglion cells without atypia or increased cellularity, and with no mitosis or necrosis seen. Our case highlights the consideration of ganglioneuroma with fatty infiltration in the differential diagnosis of a fatty tumor in the mediastinum or retroperitoneum. Additionally, our report differentiates multifocal ganglioneuroma with fatty infiltration from lipomatous ganglioneuroma on radiology and histopathology.

Keywords: Case report; Computed tomography; Ganglioneuroma; Retroperitoneum

DOI: https://doi.org/10.1159/000534060