The second line of research was done in vivo and involves targeting PD-1, a negative regulator of the immune system's response that contributes to impaired viral clearance; treatment of 8 PML patients with Pembrolizumab (123), an inhibitor of PD-1, resulted in the activation of CD4+ and CD8+ activity, reduction of JCPyV viral load and clinical improvement or stabilization of the disease in five of them, but no meaningful change was observed in the remaining three. This evidence concerns the gene CD8A and progressive multifocal leukoencephalopathy.