Low-dose lenalidomide modulates PD-L1 expression on MM tumor cells. (A) The MM cell line RPMI8226 expresses high levels of PD-L1; however, after culture for 24 hours in lenalidomide (5nM), expression was markedly reduced (baseline, MFI 174 ± 30 vs lenalidomide-treated MFI, 47 ± 35; P = .01) without effect on cell viability (n = 3 independent experiments, top panel is representative result, bottom panel is MRFI of PD-L1 expression at baseline and in lenalidomide-treated cells). (B) We confirm previous observations that PD-L1 is uniquely expressed on CD38⁺CD138⁺ primary malignant plasma cells in whole-marrow aspirates (representative finding from n = 3 MM patients). (C) As in cell line experiments, lenalidomide (5nM) down-regulates PD-L1 expression without affecting cell viability (top panel is representative finding from n = 3 MM patients, bottom panel is MRFI of PD-L1 on control- and lenalidomide-treated cells, and dotted lines are isotype controls).