Effects of Beta-Blockers on Melanoma Microenvironment and Disease Survival in Human

• Main Authors: Ludovic Jean Wrobel, Angèle Gayet-Ageron, Frédérique-Anne Le Gal
• Format: Article
• Language: English
• Published: MDPI AG 2020-04-01
• Series: Cancers
• Subjects: melanoma; beta-blocker; anti-tumor immune response; survival
• Online Access: https://www.mdpi.com/2072-6694/12/5/1094
• ISSN: 2072-6694

<i>Background:</i> The regulation of melanoma by noradrenergic signaling has gain attention since pre-clinical and clinical studies suggested a benefit of using beta-blockers to control disease progression. We need to confirm that human melanoma recapitulates the mechanisms described from pre-clinical models. <i>Methods:</i> The sources and targets of norepinephrine in the microenvironment of 20 human melanoma samples was investigated using immunostaining. The effect of an exposure to beta-blockers on immune cell type distribution and expression of immune response markers was assessed with immunostaining on 212 human primary melanoma. A statistical analysis explored the effect of an exposure to beta-blockers on progression free survival, melanoma related survival, and overall survival on the 286 eligible patients. <i>Results:</i> Tumor cells and macrophages may be a source of norepinephrine in melanoma microenvironment. Tumors from patients exposed to wide spectrum beta-blockers recapitulate the increased infiltration of T-lymphocytes and the increased production of granzyme B observed in pre-clinical models. An exposure to beta-blockers is associated with a better outcome in our cohort of melanoma patients. <i>Conclusion:</i> This study shows the association between an exposure to wide spectrum beta-blockers and markers of an effective anti-tumor immune response as well as the protective effect of beta-blockers in human melanoma patients.