CCR4 and melanoma: A set of risk factors has been explicitly linked to the development of melanoma brain metastases, including: male gender, age over 60 years, primary disease from mucosal surfaces or skin of the head, neck, scalp or trunk; acral, lentiginous, or nodular tumor histology; high Clark’s level/Breslow thickness of the primary disease; occurrence of visceral or nodal metastases; unknown primary melanomas; increased serum lactate dehydrogenase (LDH) levels; presence of oncogenic BRAF and NRAS mutations; expression of CCR4 on melanoma cells; and activation of PI3K/AKT signaling pathway16,31,44.