In a phase 1 clinical trial combining ipilimumab and the VEGF inhibitor bevacizumab (NCT00790010), the ECs of metastatic melanoma patients exhibited enhanced ICAM-1 and VCAM-1 expression post-treatment compared to pre-treatment, resulting in enhanced CD8+ T-cell infiltration.79 Another multi-targeted VEGFR kinase inhibitor, lenvatinib, which is Food and Drug Administration approved for thyroid cancer but has only had modest activity in melanoma, is currently in combination therapy trial with the anti-PD-1 drug pembrolizumab (NCT02501096). This evidence concerns the gene CD8A and metastatic melanoma.