SPDL1 and in situ carcinoma: Consistent with the increase of astrocytic PD-L1 and the upregulation of metalloproteases that cleave PD-L1 into its soluble form during EAE (Supplementary Fig. 1f), levels of sPD-L1 were significantly increased in the CSF of patients with clinically isolated syndrome (CIS) and relapsing-remitting MS (RRMS), but not during progressive disease stages (Fig. 1g and Table 1).