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Checkpoint inhibitors for the treatment of JC virus-related progressive multifocal leukoencephalopathy
1Translational Neuroradiology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.
Insights
Checkpoint blockade shows promise for treating progressive multifocal leukoencephalopathy (PML), a fatal brain infection. This approach may restore immune function when other treatments fail, but larger studies are needed.
Area of Science:
- Neuroimmunology
- Viral Infections
- Oncology
Background:
- Progressive multifocal leukoencephalopathy (PML) is a severe brain infection caused by the JC polyomavirus (JCV).
- PML predominantly affects individuals with compromised cellular immunity.
- Immune exhaustion, driven by immune checkpoints, impairs T cell responses against JCV in PML patients.
Purpose of the Study:
- To evaluate the potential of immune checkpoint blockade as a therapeutic strategy for PML.
- To explore the efficacy of restoring immune function in PML patients unresponsive to other treatments.
Main Methods:
- Review of recent case reports and clinical observations of checkpoint blockade in PML treatment.
- Analysis of the role of immune checkpoints in JCV infection and T cell dysfunction.
Main Results:
- Checkpoint blockade has demonstrated positive responses in some PML cases, particularly when immune reconstitution is challenging.
- Evidence suggests that reinvigorating T cell effector function can combat JCV infection.
Conclusions:
- Immune checkpoint blockade represents a potential therapeutic avenue for PML.
- Further large-scale studies are essential to confirm efficacy and identify predictors of response to checkpoint blockade in PML.
Abstract:
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.
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