Vojvodic Aleksandra, Vojvodic Petar, Vlaskovic-Jovicevic Tatjana, Sijan Goran, Dimitrijevic Sanja, Peric-Hajzler Zorica, Matovic Dusica, Wollina Uwe, Tirant Michael, Thuong Nguyen Van, Fioranelli Massimo, Lotti Torello
Department of Dermatology and Venereology, Military Medical Academy, Belgrade, Serbia.
Clinic for Psychiatric Disorders "Dr. Laza Lazarevic", Belgrade, Serbia.
Open Access Maced J Med Sci. 2019 Aug 30;7(18):3110-3112. doi: 10.3889/oamjms.2019.781. eCollection 2019 Sep 30.
Understanding the mechanisms of cancer immune-tolerance is one of the most important challenges. Several studies have demonstrated the potential anticarcinogenic effects of beta-blockers, in patients with prostate cancer, breast cancer, and melanoma. At the other side variety of dermatoses may be caused or aggravated by β-blockers-psoriasis, lichen planus-like drug eruptions (LDE), acrocyanosis, alopecia etc. Beta-blockers have been shown to improve the prognosis of melanoma patients significantly. Propranolol inhibits melanoma by downregulating the tumour angiogenesis but also tumour cell proliferation, invasiveness and local immune suppression. Studies showed that only β3-but, not β2-adrenoceptors, were up-regulated under hypoxia in peripheral blood mononuclear cells and selectively expressed in immune cell sub-populations including Treg, MDSC, and NK. They increased NK and CD8 number and cytotoxicity. Catecholamines may retard melanoma progression and that β-blockers may have unrecognised potential as a therapeutic intervention for melanoma, in the prevention of the growth of melanoma in all stages and as adjuvant therapy with other targeted and immune therapies for melanoma.
了解癌症免疫耐受机制是最重要的挑战之一。多项研究已证明β受体阻滞剂对前列腺癌、乳腺癌和黑色素瘤患者具有潜在的抗癌作用。另一方面,多种皮肤病可能由β受体阻滞剂引起或加重,如银屑病、扁平苔藓样药疹(LDE)、手足发绀症、脱发等。已表明β受体阻滞剂可显著改善黑色素瘤患者的预后。普萘洛尔通过下调肿瘤血管生成以及肿瘤细胞增殖、侵袭和局部免疫抑制来抑制黑色素瘤。研究表明,在外周血单核细胞中,仅β3而非β2肾上腺素能受体在缺氧状态下上调,并在包括调节性T细胞(Treg)、髓源性抑制细胞(MDSC)和自然杀伤细胞(NK)在内的免疫细胞亚群中选择性表达。它们增加了NK细胞和CD8细胞的数量及细胞毒性。儿茶酚胺可能会延缓黑色素瘤进展,并且β受体阻滞剂在预防黑色素瘤各阶段生长以及作为黑色素瘤其他靶向治疗和免疫治疗的辅助治疗方面可能具有未被认识到的治疗干预潜力。