Melanoma treatment is moving toward ICI-based combinations with anti-angiogenic agents, a promising paradigm that warrants deeper research to refine patient selection and improve outcomes.

While the approach carries risks of cardiovascular and dermatologic adverse events, these can be mitigated through careful monitoring and supportive care.

Preclinical evidence suggests the combination reverses tumor immunosuppression by remodeling tumor vasculature and shifting immune cell dynamics to enhance antitumor activity.

Future directions call for biomarker discovery to improve patient stratification and the development of precision, individualized strategies to maximize survival benefits.

The article is a mini-review in Frontiers in Immunology examining how ICIs and anti-angiogenic agents synergize in melanoma, covering mechanisms, preclinical data, and clinical evidence.

The combination modulates the tumor immune microenvironment by impacting checkpoints and angiogenic factors like VEGF and ANG-2, promoting vascular normalization and greater T-cell infiltration.

Clinical data show ICI plus anti-angiogenic therapy outperforms ICI alone across melanoma subtypes (advanced, mucosal, acral, and brain-metastatic), with an overall safety profile that is manageable through multidisciplinary care.