bims-netuvo 2022-08-28 papers

Issue of 2022‒08‒28
five papers selected by
Maksym V. Kopanitsa
The Francis Crick Institute

Discov Oncol. 2022 Aug 23. 13(1): 80

Neuroimmune crosstalk and its impact on cancer therapy and research.

Cancer is a major health problem as it is the first or second leading cause of death worldwide. The global cancer burden is expected to rise 47% relative to 2020 cancer incidence. Recently, the fields of neuroscience, neuroimmunology and oncology have elaborated the neuroimmune crosstalk role in tumor initiation, invasion, progression, and metastases. The nervous system exerts a broad impact on the tumor microenvironment by interacting with a complex network of cells such as stromal, endothelial, malignant cells and immune cells. This communication modulates cancer proliferation, invasion, metastasis, induce resistance to apoptosis and promote immune evasion. This paper has two aims, the first aim is to explain neuroimmune crosstalk in cancer, tumor innervation origin and peripheral nervous system, exosomes, and miRNA roles. The second aim is to elaborate neuroimmune crosstalk impact on cancer therapy and research highlighting various potential novel strategies such as use of immune checkpoint inhibitors and anti-neurogenic drugs as single agents, drug repurposing, miRNA-based and si-RNA-based therapies, tumor denervation, cellular therapies, and oncolytic virus therapy.

Keywords: Anti-neurogenic drugs; Drug repurposing; Exosomes; Neuroimmune crosstalk; Oncolytic virus therapy; Tumor innervation; miRNA

DOI: https://doi.org/10.1007/s12672-022-00547-5

Antioxid Redox Signal. 2022 Aug 26.

Novel anticancer strategy by targeting the gut microbial neurotransmitter signaling to overcome immunotherapy resistance.

Elaine Lai-Han Leung, Jumin Huang, Junmin Zhang, Juanhong Zhang, Meifang Wang, Yingjie Zhu, Zhiqiang Meng, Haijie Yu, Erwin Neher, Lijuan Ma, Xiao-Jun Yao.

SIGNIFICANCE: Microbial neurotransmitters, as potential targets for cancer therapy, are expected to provide a new perspective on the interaction between the gut microbiome and cancer immunotherapy. Recent Advance: Mounting data reveal that most neurotransmitters can be derived from gut microbiota. Furthermore, modulation of neurotransmitter signaling can limit tumor growth and enhance antitumor immunity.CRITICAL ISSUES: Here, we first present the relationships between microbial neurotransmitters and cancer cells mediated by immune cells. Then, we discuss the microbial neurotransmitters recently associated with cancer immunotherapy. Notably, the review emphasizes that neurotransmitter signaling plays a substantial role in cancer immunotherapy as an emerging cancer treatment target by regulating targeted receptors and interfering with the tumor microenvironment.
FUTURE DIRECTIONS: Future studies are required to uncover the antitumor mechanisms of neurotransmitter signaling to develop novel treatment strategies to overcome cancer immunotherapy resistance.

DOI: https://doi.org/10.1089/ars.2021.0243

Ann Thorac Surg. 2022 Aug 23. pii: S0003-4975(22)01120-1. [Epub ahead of print]

Lymphovascular and Perineural Invasion after Neoadjuvant Therapy in Esophageal Squamous Carcinoma.

Jianfeng Zhou, Yushang Yang, Hanlu Zhang, Siyuan Luan, Xin Xiao, Xiaokun Li, Pinhao Fang, Yimin Gu, Longqi Chen, Xiaoxi Zeng, Yong Yuan.

BACKGROUND: Lymphovascular invasion and perineural invasion are unfavorable prognostic factors in patients with esophageal squamous cell carcinoma. However, the prevalence and prognostic importance of lymphovascular invasion and perineural invasion after neoadjuvant chemoradiotherapy in these patients remains unclear.METHODS: We retrospectively reviewed specimens of 321 patients with pathologically diagnosed esophageal squamous cell carcinoma who underwent neoadjuvant chemoradiotherapy in our institution from 2017-2020. Lymphovascular invasion and perineural invasion were assessed by hematoxylin and eosin staining. Survival was analyzed using the log-rank test and multivariable Cox regression analysis.
RESULTS: Lymphovascular invasion and perineural invasion were present in 12.5% (n=40) and 17.8% (n=57) of resection specimens, respectively. Lymphovascular invasion and perineural invasion were significantly more common in patients with advanced cancer (both p < 0.05). In the univariate analyses, lymphovascular invasion and perineural invasion were associated with shorter overall survival and disease-free survival. Multivariable analysis revealed that lymphovascular invasion after neoadjuvant therapy was an independent adverse prognostic factor for overall survival and disease-free survival. Subgroup analyses showed lymphovascular invasion could identify cases with worse overall survival or disease-free survival among node-negative patients, indicating the role of lymphovascular invasion in the precise staging of pN0 patients.
CONCLUSIONS: Lymphovascular invasion and perineural invasion were significantly negatively correlated with overall survival and disease-free survival. Lymphovascular invasion was an independent prognostic predictor in esophageal squamous cell carcinoma patients after neoadjuvant chemoradiotherapy. Lymphovascular invasion and perineural invasion should be considered in the histopathology workup for esophageal squamous cell carcinoma patients after neoadjuvant chemoradiotherapy.

Keywords: esophageal cancer(1); lymphovascular invasion(3); neoadjuvant therapy(2); perineural invasion(4); prognosis(5)

DOI: https://doi.org/10.1016/j.athoracsur.2022.07.052

Respirol Case Rep. 2022 Sep;10(9): e01023

A case of schwannoma at the origin of the right recurrent laryngeal nerve resected under uniportal video-assisted thoracic surgery.

Go Kamimura, Kazuhiro Ueda, Aya Takeda, Koki Maeda, Masaya Aoki, Masami Sato.

Mediastinal neurogenic tumours are mostly derived from sympathetic nerves and intercostal nerves, and vagus nerve-derived schwannomas are rare. We encountered a tumour originating from the origin of the recurrent laryngeal nerve that was accompanied by the azygos lobe, which made it difficult to approach; it was ultimately able to be removed via uniportal video-assisted thoracic surgery. This case involved a 63-year-old female patient. There were no particular symptoms, but an abnormal chest shadow was noted on an imaging examination. Chest imaging revealed a smooth-surfaced mass in the upper right mediastinum with the azygos lobe. A diagnosis of schwannoma was made by imaging, and the patient underwent resection via uniportal video-assisted thoracic surgery. The tumour, which originated from the origin of the right recurrent laryngeal nerve, was sharply removed without causing recurrent laryngeal nerve palsy.

Keywords: azygos lobe; recurrent laryngeal nerve; schwannoma; uniportal video‐assisted thoracic surgery

DOI: https://doi.org/10.1002/rcr2.1023

Am J Physiol Regul Integr Comp Physiol. 2022 Aug 22.

Ovarian status modulates endocrine and neuroinflammatory responses to a murine mammary tumor.

Lindsay D Strehle, Kathryn L G Russart, Valerie A Burch, Corena V Grant, Leah M Pyter.

Breast cancer patients have increased circulating inflammatory markers and mammary tumors increase neuroinflammation in rodent models. Menopausal status is not only important in the context of breast cancer as circulating estrogen influences tumor progression, but also because estrogen is anti-inflammatory and an essential modulator of endocrine function in the brain and body. Here, we manipulated "menopause" status (ovary-intact and ovariectomized) in an ER+ mouse mammary tumor model to determine the extent to which ovarian status modulates: 1) tumor effects on estrogen concentrations and signaling in the brain, 2) tumor effects on estrogen-associated neurobiology and inflammation, and 3) the ability for tumor resection to resolve the effects of a tumor. We hypothesized that reduced circulating estradiol (E2) following ovariectomy exacerbates tumor-induced peripheral and central inflammation. Notably, we observed ovarian-dependent modulation on tumor-induced peripheral outcomes, including E2-dependent processes and, to a lesser degree, circulating inflammatory markers. In the brain, ovariectomy exacerbated neuroinflammatory markers in select brain regions and modulated E2-related neurobiology due to a tumor and/or resection. Overall, our data suggest that ovarian status has moderate implications for tumor-induced alterations in neuroendocrinology and neuroinflammation and mild effects on peripheral inflammatory outcomes in this murine mammary tumor model.

Keywords: brain; breast cancer; cytokines; estrogen; tumor resection

DOI: https://doi.org/10.1152/ajpregu.00124.2022