PD-1: More Than Immunity in Melanoma

Much has been made recently of the therapeutic benefits of PD-1 blockade. However, is the protein itself contributing to melanoma progression? A group of investigators set out to answer this question using several sophisticated mouse models.

The authors show that established melanoma cell lines from both humans and mouse, and melanoma tumor specimens from humans, all contained PD-expressing melanoma cells. Overexpression of PD-1 in melanomas enhanced the growth of the cancer, even in the absence of immunity. Similarly, reducing PD-1 or mutagenesis of the PD-1 signaling motifs also led to a suppression of tumor growth, even without host immunity. When PD-1 binds its ligand, PD-L1, the mTOR signaling pathway is also activated.