title: Propranolol induces a favourable shift of anti-tumor immunity in a murine spontaneous model of melanoma.
abstract: In a previous study on a xenograft model of melanoma, we showed that the beta-adrenergic receptor antagonist propranolol inhibits melanoma development by modulating angiogenesis, proliferation and cell survival. Stress hormones can influence tumor development in different ways and norepinephrine was shown to downregulate antitumor immune responses by favoring the accumulation of immunosuppressive cells, impairing the function of lymphocytes. We assessed the effect of propranolol on antitumor immune response in the MT/Ret mouse model of melanoma. Propranolol treatment delayed primary tumor growth and metastases development in MT/Ret mice. Consistent with our previous observations in human melanoma xenografts, propranolol induces a decrease in cell proliferation and vessel density in the primary tumors and in metastases. In this immunocompetent model, propranolol significantly reduced the infiltration of myeloid cells, particularly neutrophils, in the primary tumor. Inversely, cytotoxic tumor infiltrating lymphocytes were more frequent in the tumor stroma of treated mice. In a consistent manner, we observed the same shift in the proportions of infiltrating leukocytes in the metastases of treated mice. Our results suggest that propranolol, by decreasing the infiltration of immunosuppressive myeloid cells in the tumor microenvironment, restores a better control of the tumor by cytotoxic cells.
authors: Hôpitaux Universitaires de Genève, Service de Dermatologie, Genève, Switzerland.
authors: Ludovic
authors: L
authors: Jean Wrobel
authors: Inserm, U1016, Institut Cochin, Paris, France.|CNRS, UMR8104, Paris, France.|Université Paris Descartes, Paris, France.
authors: Lloyd
authors: L
authors: Bod
authors: Inserm, U1016, Institut Cochin, Paris, France.|CNRS, UMR8104, Paris, France.|Université Paris Descartes, Paris, France.
authors: Renée
authors: R
authors: Lengagne
authors: Department of Occupational and Environmental Health, Nagoya University Graduate School of Medicine, Aichi, Japan.
authors: Masashi
authors: M
authors: Kato
authors: Inserm, U1016, Institut Cochin, Paris, France.|CNRS, UMR8104, Paris, France.|Université Paris Descartes, Paris, France.
authors: Armelle
authors: A
authors: Prévost-Blondel
authors: Hôpitaux Universitaires de Genève, Service de Dermatologie, Genève, Switzerland.
authors: Frédérique-Anne
authors: FA
authors: Le Gal
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D016246:Lymphocytes, Tumor-Infiltrating / Q000187:drug effects; D008546:Melanoma, Experimental / Q000188:drug therapy* / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D009362:Neoplasm Metastasis; D011433:Propranolol / Q000008:administration & dosage* / Q000494:pharmacology; D051096:Proto-Oncogene Proteins c-ret / Q000235:genetics; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000276:immunology; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D011433:Propranolol; D051096:Proto-Oncogene Proteins c-ret; C494999:Ret protein, mouse
keywords: anti-tumor immunity; beta-blocker; melanoma; norepinephrine; propranolol