β -Adrenoceptor As a Potential Immuno-suppressor Agent in Melanoma

Overview

Journal Br J Pharmacol

Publisher Wiley

Specialty Pharmacology

Date 2019 Mar 16

PMID 30874296

Citations 43

Authors

Maura Calvani

Gennaro Bruno

Massimo Dal Monte

Romina Nassini

Filippo Fontani

Arianna Casini

Lorenzo Cavallini

Matteo Becatti

Francesca Bianchini

Francesco De Logu

Giulia Forni

Giancarlo la Marca

Lido Calorini

Paola Bagnoli

Paola Chiarugi

Alberto Pupi

Chiara Azzari

Pierangelo Geppetti

Claudio Favre

Luca Filippi

Affiliations

Soon will be listed here.

Abstract

Background And Purpose: Stress-related catecholamines have a role in cancer and β-adrenoceptors; specifically, β -adrenoceptors have been identified as new targets in treating melanoma. Recently, β -adrenoceptors have shown a pleiotropic effect on melanoma micro-environment leading to cancer progression. However, the mechanisms by which β -adrenoceptors promote this progression remain poorly understood. Catecholamines affect the immune system by modulating several factors that can alter immune cell sub-population homeostasis. Understanding the mechanisms of cancer immune-tolerance is one of the most intriguing challenges in modern research. This study investigates the potential role of β -adrenoceptors in immune-tolerance regulation.

Experimental Approach: A mouse model of melanoma in which syngeneic B16-F10 cells were injected in C57BL-6 mice was used to evaluate the effect of β-adrenoceptor blockade on the number and activity of immune cell sub-populations (Treg, NK, CD8, MDSC, macrophages, and neutrophils). Pharmacological and molecular approaches with β-blockers (propranolol and SR59230A) and specific β-adrenoceptor siRNAs targeting β - or β -adrenoceptors were used.

Key Results: Only β -, but not β -adrenoceptors, were up-regulated under hypoxia in peripheral blood mononuclear cells and selectively expressed in immune cell sub-populations including Treg, MDSC, and NK. SR59230A and β -adrenoceptor siRNAs increased NK and CD8 number and cytotoxicity, while they attenuated Treg and MDSC sub-populations in the tumour mass, blood, and spleen. SR59230A and β -adrenoceptor siRNAs increased the ratio of M1/M2 macrophages and N1 granulocytes.

Conclusions And Implications: Our data suggest that β -adrenoceptors are involved in immune-tolerance, which opens the way for new strategic therapies to overcome melanoma growth.

Linked Articles: This article is part of a themed section on Adrenoceptors-New Roles for Old Players. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.14/issuetoc.

Citing Articles

Protective Effects of Beta-3 Adrenoceptor Agonism on Mucosal Integrity in Hyperoxia-Induced Ileal Alterations.

Nardini P, Zizi V, Molino M, Fazi C, Calvani M, Carrozzo F Antioxidants (Basel). 2024; 13(7).

PMID: 39061931 PMC: 11273805. DOI: 10.3390/antiox13070863.

β3-adREnoceptor Analysis in CORD Blood of Neonates (β3 RECORD): Study Protocol of a Pilot Clinical Investigation.

Scaramuzzo R, Crucitta S, Del Re M, Cammalleri M, Bagnoli P, Dal Monte M Life (Basel). 2024; 14(6).

PMID: 38929758 PMC: 11204445. DOI: 10.3390/life14060776.

Preimmunization with Listeria-vectored cervical cancer vaccine candidate strains can establish specific T-cell immune memory and prevent tumorigenesis.

Zhang Y, Liu S, Chen M, Ou Q, Tian S, Tang J BMC Cancer. 2024; 24(1):288.

PMID: 38439023 PMC: 10910769. DOI: 10.1186/s12885-024-12046-7.

Inside the Biology of the β3-Adrenoceptor.

Pasha A, Tondo A, Favre C, Calvani M Biomolecules. 2024; 14(2).

PMID: 38397396 PMC: 10887351. DOI: 10.3390/biom14020159.

β3 Adrenoceptor Agonism Prevents Hyperoxia-Induced Colonic Alterations.

Filippi L, Nardini P, Zizi V, Molino M, Fazi C, Calvani M Biomolecules. 2023; 13(12).

PMID: 38136626 PMC: 10741994. DOI: 10.3390/biom13121755.

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