Checkpoint inhibitors for the treatment of JC virus-related progressive multifocal leukoencephalopathy.

Progressive multifocal leukoencephalopathy (PML) is a frequently fatal brain infection caused by the JC polyomavirus (JCV). PML occurs in people with impaired cellular immunity, and the only effective treatment is restoration of immune function. Infection in immunocompromised hosts is often associated with immune exhaustion, which is mediated by inhibitory cell surface receptors known as immune checkpoints, leading to loss of T cell effector function. Blockade of immune checkpoints can reinvigorate host responses to fight infection. Recently, there have been several reports of checkpoint blockade to treat PML in patients in whom immune reconstitution is otherwise not possible, with some evidence for positive response. Larger studies are needed to better understand efficacy of checkpoint blockade in PML and factors that determine response.