Achille Aouba, France
CHU de Caen ImmunologyPresenter of 1 Presentation
RATIONALE AND EFFICACY OF PROGRAMMED CELL DEATH-1–TARGETING TO TREAT PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY
Abstract
Background and Aims
Progressive multifocal leukoencephalopathy (PML), an opportunistic JCV infection with poor prognosis, has no effective treatment. Programmed cell death-1 (PD-1) and its ligand (PD-L1) function as T-cell co-inhibitors, pivotal in the T-cell–exhaustion pathway frequently involved in chronic viral infections.
Methods
Hypothesizing that PD-1 blockade might abrogate T-cell exhaustion, and control JCV replication and PML course, we gave a 53-year-old PML patient nivolumab salvage therapy.
Results
All clinical and imaging signs regressed, with only residual sequelae, and JCV was completely cleared from cerebrospinal fluid. No immune reconstitution inflammatory syndrome or related adverse events occurred.
Analyses of the T-cell infiltrate and PD-1/PD-L1 expression in a pretreatment brain biopsy showed: intense PD-L1 expression on CD163+ parenchymal macrophages; high PD-1 expression on CD4+ and CD8+ T cells; and PD-L1+ macrophage and T-cell co-localization, supporting their partnership in immune exhaustion and virus escape. tory syndrome or related adverse events occurred.
Conclusions
To conclude, targeting an immune checkpoint, e.g. PD-1, to boost host defenses against JCV appears to be a promising and safe therapeutic option for PML but requires prospective studies.