Effects of Beta-Blockers on Melanoma Microenvironment and Disease Survival in Human.
Ludovic Jean WrobelAngèle Gayet-AgeronFrédérique-Anne Le GalPublished in: Cancers (2020)
Background: 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. Methods: 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. Results: 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. Conclusion: 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.
Keyphrases
- end stage renal disease
- endothelial cells
- immune response
- ejection fraction
- newly diagnosed
- chronic kidney disease
- angiotensin converting enzyme
- free survival
- stem cells
- prognostic factors
- skin cancer
- induced pluripotent stem cells
- inflammatory response
- high resolution
- basal cell carcinoma
- single molecule
- drug induced