Venlafaxine suppressed PD-L1 expression through oxidative stress and improved anti-tumor immune responses in melanoma mice

Melanoma is an aggressive cutaneous malignancy characterized by high metastatic potential and poor prognosis. Oxidative stress plays a pivotal role in melanoma pathogenesis, as tumor cells exploit Reactive Oxygen Species (ROS) to promote survival, drive progression, and regulate critical signaling pathways-including the expression of programmed death-ligand 1 (PD-L1), a key immune checkpoint molecule that facilitates immune evasion. This study aimed to investigate whether venlafaxine, a compound with known biological activities, could modulate oxidative stress to suppress PD-L1 expression and enhance anti-tumor immune responses in melanoma. In vitro experiments demonstrated that venlafaxine significantly inhibited melanoma cell proliferation and migration, accompanied by a marked reduction in intracellular ROS production and altered expression of PD-L1-related proteins. In a murine melanoma model, venlafaxine administration effectively retarded tumor growth, downregulated PD-L1 levels in tumor tissues, promoted the infiltration of T lymphocytes into the tumor microenvironment, and increased the proportion of T lymphocytes in the spleen. Collectively, these findings indicate that venlafaxine exerts anti-melanoma effects by mitigating ROS release and potentiating anti-tumor immune responses, thereby highlighting its potential as a therapeutic candidate for melanoma treatment.

PD-L1; melanoma; oxidative stress; venlafaxine.