In a small clinical trial with six melanoma patients, immunization with a personalized neoantigen-based synthetic vaccine induced polyfunctional CD4 T-cell responses more frequently than CD8 T-cell responses (60% versus 16%, respectively), which were associated with a complete response in four patients, while the two patients who progressed subsequently responded to immune checkpoint blockade with anti-PD-1 [185]. This evidence concerns the gene PDCD1 and melanoma.