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Adrenergic Signaling in Immunotherapy of Cancer: Friend or Foe?

ABSTRACT: The incidence of cancer is increasing worldwide, which is to a large extent related to the population's increasing lifespan. However, lifestyle changes in the Western world are causative as well. Exercise is intrinsically associated with what one could call a "healthy life", and physical activity is associated with a lower risk of various types of cancer. Mouse models of exercise have shown therapeutic efficacy across numerous cancer models, at least in part due to the secretion of adrenaline, which mobilizes cells of the immune system, i.e., cytotoxic T and natural killer (NK) cells, through signaling of the ?-2 adrenergic receptor (?2AR). Clinical trials aiming to investigate the clinical value of exercise are ongoing. Strikingly, however, the use of ?-blockers-antagonists of the very same signaling pathway-also shows signs of clinical potential in cancer therapy. Cancer cells also express ?-adrenergic receptors (?ARs) and signaling of the receptor is oncogenic. Moreover, there are data to suggest that ?2AR signaling in T cells renders the cell functionally suppressed. In this paper, we discuss these seemingly opposing mechanisms of cancer therapy-exercise, which leads to increased ?2AR signaling, and ?-blocker treatment, which antagonizes that same signaling-and suggest potential mechanisms and possibilities for their combination.

SUBMITTER: Jensen AWP

PROVIDER: S-EPMC7866099 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Adrenergic Signaling in Immunotherapy of Cancer: Friend or Foe?

Jensen Agnete Witness Praest AWP Carnaz Simões Ana Micaela AM Thor Straten Per P Holmen Olofsson Gitte G

Cancers 20210121 3

The incidence of cancer is increasing worldwide, which is to a large extent related to the population's increasing lifespan. However, lifestyle changes in the Western world are causative as well. Exercise is intrinsically associated with what one could call a "healthy life", and physical activity is associated with a lower risk of various types of cancer. Mouse models of exercise have shown therapeutic efficacy across numerous cancer models, at least in part due to the secretion of adrenaline, w ...[more]

PMID: 33494360

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Project description:Cancer remains the leading cause of death worldwide with close to 10 million deaths reported annually. Due to growth of the advanced age cohort in our population, it is predicted that the number of new cancer cases diagnosed between now until 2035 is to reach potentially 24 million individuals, a staggering increase in a relatively short time period. For many solid tumors, surgical resection along with chemotherapy is the best available approach to a potential cure which leads to almost 80% of cancer patients undergoing at least one surgical procedure during the course of their disease. During surgical intervention, the exposure to general anesthesia can be lengthy, complex and often involves various modalities resulting in an important question as to the role, if any, anesthesia may play in primary recurrence or metastatic conversion. Many components of the stress and inflammatory responses exhibited in the perioperative period can contribute to cancer growth and invasion. The agents used to induce and maintain general anesthesia have variable interactions with the immune and neuroendocrine systems and can influence the stress response during surgery. Thus, debating the best type of anesthesia that would help to attenuate sympathetic and/or pro-inflammatory responses while modulating cytokine release and transcription factors/oncogenes remains at the forefront. This may affect inducible cancer cell survival and migratory abilities not only intra-operatively, but also during the immediate post-operative phase of recovery. The ultimate question becomes how and whether the choice of anesthesia may influence the outcomes of cancer surgery with two major approaches being considered, i.e., regional and general anesthesia as well as the various hypnotics, analgesics and sympatholytics commonly used. In this review, we will address the latest information as to the role that anesthesia may play during cancer surgery with specific focus on primary recurrence and metastasis.

Project description:BackgroundGastric cancer (GC) remains a common disease with a poor prognosis worldwide. The SET binding protein 1 (SETBP1) has been implicated in the pathogenesis of several cancers and plays a dual role as an oncogene and a tumor suppressor gene. However, the role and underlying mechanism of SETBP1 in GC remain unclear.Materials and methodsWe used next-generation RNA sequencing (RNA-seq) data from The Cancer Genome Atlas (TCGA) to explore the correlation between SETBP1 expression and tumor progression. We then quantified SETBP1 expression in GC cells with real-time quantitative polymerase chain reactions (RT-qPCR). The chi-square test and logistic regression were used to assess the correlation between SETBP1 expression and clinicopathological features. Kaplan-Meier survival analysis and Cox proportional hazards regression model were used to assess the relationship between SETBP1 expression and survival. Finally, gene set enrichment analyses (GSEA) were used to examine GC-related signaling pathways in low and high SETBP1 expressing samples.ResultsWe found SETBP1 expression levels in GC tissues to be significantly lower than in adjacent non-tumor tissues in the TCGA database. In addition, SETBP1 expression differed significantly between groups classified by tumor differentiation. Furthermore, SETBP1 expression in diffuse-type GC was significantly higher than in intestinal-type GC. However, it did not differ significantly across pathological- or T-stage groups. RT-qPCR and comprehensive meta-analysis showed that SETBP1 expression is downregulated in GC cells and tissues. Interestingly, SETBP1 expression in poorly- or un-differentiated GC cells was higher than in well-differentiated GC cells. Moreover, the chi-square test and logistic regression analyses showed that SETBP1 expression correlates significantly with tumor differentiation. Kaplan-Meier curves indicated that patients with relatively high SETBP1 expression had a poor prognosis. Multivariate analyses indicated that SETBP1 expression might be an important predictor of poor overall survival in GC patients. GSEA indicated that 20 signaling pathways were significantly enriched in samples with high and low SETBP1 expression.ConclusionSETBP1 may play a dual role in GC progression.

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Adrenergic Signaling in Immunotherapy of Cancer: Friend or Foe?

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Adrenergic Signaling in Immunotherapy of Cancer: Friend or Foe?

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