Our results suggest that PML may result from two nonexclusive mechanisms: (i) the failure of JCV‐specific T‐cell response consecutive to the inhibition of PD1‐PDL1 pathway, as no compensatory overexpression of other inhibitory receptors on patient T cells was observed and (ii) a neuroinflammation (PML‐IRIS) that may have led to virus reactivation and replication. Here, PML is linked to progressive multifocal leukoencephalopathy.