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

Melanoma is an aggressive cutaneous malignancy characterised by high metastatic potential and poor prognosis. Oxidative stress plays a pivotal role in melanoma pathogenesis, as tumour cells exploit reactive oxygen species (ROS) to promote survival, drive progression, and regulate critical signalling 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-tumour immune responses in melanoma. <i>In vitro</i> 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 tumour growth, downregulated PD-L1 levels in tumour tissues, promoted the infiltration of T lymphocytes into the tumour 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-tumour immune responses, thereby highlighting its potential as a therapeutic candidate for melanoma treatment.