β2-adrenergic receptor signaling regulates metabolic pathways critical to myeloid-derived suppressor cell function within the TME

Mohammadpour, Hemn; MacDonald, Cameron R.; McCarthy, Philip L.; Abrams, Scott I.; Repasky, Elizabeth A.

doi:10.1016/j.celrep.2021.109883

Cited by 59 publications

(53 citation statements)

References 59 publications

(74 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Approaches to target dysfunctional lipid metabolism show prospects (Bian et al, 2021). Recent studies also have mentioned the regulation among NRGs, immune response, and cellular metabolism (Jensen et al, 2021;Mohammadpour et al, 2021;Wan et al, 2021). Apart from Frontiers in Cell and Developmental Biology frontiersin.org that, drug prediction revealed that benzimidazole-related and vinca-alkaloid-related drugs could effectively reverse these changes.…”

Section: Discussionmentioning

confidence: 99%

Comprehensive analysis to identify the neurotransmitter receptor-related genes as prognostic and therapeutic biomarkers in hepatocellular carcinoma

Wang

Shi

et al. 2022

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

Background: Hepatocellular carcinoma (HCC) is a highly heterogeneous disease with high morbidity and mortality, which accounts for the fourth most common cause of cancer-related deaths. Reports suggest that the neurotransmitter receptor-related genes (NRGs) may influence the tumor microenvironment and the prognosis of patients with HCC.Methods: The clinical information and RNA-seq data of patients with HCC were acquired from the ICGC-LIRI-JP dataset and the TCGA-LIHC dataset. Effects of 115 NRGs on the prognosis of HCC patients were analyzed in the ICGC-LIRI-JP dataset. The least absolute shrinkage and selection operator (LASSO) regression model was utilized to generate a risk score formula based on the critical NRGs. Next, the risk score effectiveness was validated both in the TCGA-LIHC dataset and in our clinical HCC samples. Based on the risk scores, patients with HCC were divided into two groups. Moreover, differentially expressed genes (DEGs) were screened. The gene ontology (GO) was used to analyze the functional enrichments of DEGs and to identify potential signaling pathways. To test the diagnostic effectiveness of our model, the receiver operator characteristic curve (ROC) analysis and nomogram were used. Finally, potential targeted drug prediction was performed based on DEGs of nine clinical HCC samples.Results: Nine NRGs were correlated significantly with the prognosis of patients with HCC, and eight NRGs were successfully included in the LASSO regression model. The Kaplan-Meier analysis of overall survival (OS) suggested that patients in the high-risk score group had worse prognosis; on the other hand, ROC analysis revealed a high prognostic value of the risk score in HCC. Several critical signaling pathways, such as lipid metabolism, organic acid metabolism, cell migration, cell adhesion, and immune response, were enriched both in public datasets and clinical samples. Nomogram results also suggested that the risk scores correlated well with the patients’ prognosis. Potential targeted drugs prediction revealed that tubulin inhibitors might be the promising drugs for patients with HCC who have high risk scores based on the NRGs.Conclusion: We established a prognostic model based on critical NRGs. NRGs show a promising prognostic prediction value in HCC and are potential therapeutic targets for the disease treatment.

show abstract

Section: Discussionmentioning

confidence: 99%

Comprehensive analysis to identify the neurotransmitter receptor-related genes as prognostic and therapeutic biomarkers in hepatocellular carcinoma

Wang

Shi

et al. 2022

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

show abstract

“…Moreover, carnitine palmitoyltransferase 1a (CPT1a) + VIDCAI + DR − M-MDSC expansion was observed in patients with severe COVID-19 ( 73 ). CPT1a is involved in fatty acid oxidation and has been correlated with the recruitment and differentiation of MDSCs ( 77 ).…”

Section: Mdscs and Covid-19mentioning

confidence: 99%

Myeloid-Derived Suppressor Cells in COVID-19: The Paradox of Good

et al. 2022

View full text Add to dashboard Cite

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the ongoing coronavirus disease 2019 (COVID-19) pandemic. Viral replication in the respiratory tract induces the death of infected cells and the release of pathogen- associated molecular patterns (PAMPs). PAMPs give rise to local inflammation, increasing the secretion of pro- inflammatory cytokines and chemokines, which attract immune cells from the blood into the infected lung. In most individuals, lung-recruited cells clear the infection, and the immune response retreats. However, in some cases, a dysfunctional immune response occurs, which triggers a cytokine storm in the lung, leading to acute respiratory distress syndrome (ARDS). Severe COVID-19 is characterized by an impaired innate and adaptive immune response and by a massive expansion of myeloid-derived suppressor cells (MDSCs). MDSCs function as protective regulators of the immune response, protecting the host from over-immunoreactivity and hyper-inflammation. However, under certain conditions, such as chronic inflammation and cancer, MDSCs could exert a detrimental role. Accordingly, the early expansion of MDSCs in COVID-19 is able to predict the fatal outcome of the infection. Here, we review recent data on MDSCs during COVID-19, discussing how they can influence the course of the disease and whether they could be considered as biomarker and possible targets for new therapeutic approaches.

show abstract

“…Experimental model systems have identified the β 2 -adrenergic pathway to be implicated in the physiological effects of stress on cancer progression. 62 , 97 , 98 , 206 - 209 Epidemiological studies in cancer patients that compared use of cardio selective versus non-selective β-blockade found a favorable effect of non-selective β-blockade. 189 , 200 Another important issue is the potential for confounding in non-randomized observational research where indication for β-blocker use is correlated with many diseases that are likely to adversely impact cancer progression.…”

Section: Pharmacologic Approaches To Reduce Stress-related Cancer Pro...mentioning

confidence: 99%

Biobehavioral Pathways and Cancer Progression: Insights for Improving Well-Being and Cancer Outcomes

et al. 2022

View full text Add to dashboard Cite

The relationship between psychosocial factors and cancer has intrigued people for centuries. In the last several decades there has been an expansion of mechanistic research that has revealed insights regarding how stress activates neuroendocrine stress-response systems to impact cancer progression. Here, we review emerging mechanistic findings on key pathways implicated in the effect of stress on cancer progression, including the cellular immune response, inflammation, angiogenesis, and metastasis, with a primary focus on the mediating role of the sympathetic nervous system. We discuss converging findings from preclinical and clinical cancer research that describe these pathways and research that reveals how these stress pathways may be targeted via pharmacological and mind-body based interventions. While further research is required, the body of work reviewed here highlights the need for and feasibility of an integrated approach to target stress pathways in cancer patients to achieve comprehensive cancer treatment.

show abstract

β2-adrenergic receptor signaling regulates metabolic pathways critical to myeloid-derived suppressor cell function within the TME

Abstract: Highlights d Tumor progression increases the expression of b2-AR on MDSCs d b2-AR signaling increases fatty acid oxidation and oxidative phosphorylation in MDSCs d b2-AR signaling in MDSCs increases autophagy-mediated PGE2 production

Cited by 59 publications

References 59 publications

Comprehensive analysis to identify the neurotransmitter receptor-related genes as prognostic and therapeutic biomarkers in hepatocellular carcinoma

Comprehensive analysis to identify the neurotransmitter receptor-related genes as prognostic and therapeutic biomarkers in hepatocellular carcinoma

Myeloid-Derived Suppressor Cells in COVID-19: The Paradox of Good

Biobehavioral Pathways and Cancer Progression: Insights for Improving Well-Being and Cancer Outcomes

Contact Info

Product

Resources

About