A new paper published in the journal Nature Communications explores programmed cell death (PD-1) in melanoma cells and the immune system's response. Immune checkpoint inhibitors are cancer fighting drugs that help the immune system do its job of detecting and attacking tumor cells. Programmed cell death 1 (PD-1) is a common target for this type of drug—it is a protein that sits on the surface of T cells and helps regulate the immune system's response to neighboring cells, both normal and cancerous.
While most research efforts to date have focused on PD-1's role in T cells, it is also active in many other kinds of cells—including cancer cells , as first demonstrated by the Schatton laboratory at Brigham and Women's Hospital. The researchers aimed to define the molecular mechanisms controlling PD-1 expression and its therapeutic targeting in melanoma cells . The team identified a melanoma cell-intrinsic type I interferon-JAK/STAT signaling circuit regulating the amount of PD-1 in tumor cells .
They further discovered that inhibition of this pathway not only reversed induction of PD-1 in melanoma cells, but also reduced the efficacy of PD-1 checkpoint therapy. The work thus cautions against combining JAK or IFNAR antagonists with PD-1 inhibitors, given that this regimen may weaken the effectiveness of immune checkpoint monotherapy. This work builds off previously published studies identifying PD-1 as a tumor cell-intrinsic growth promoting receptor in melanoma and Merkel cel.