Enhanced cross-priming of naive CD8+ T cells by dendritic cells treated by the IMiDs® immunomodulatory compounds lenalidomide and pomalidomide

Summary The IMiDsimmunomodulatory compounds lenalidomide and pomalido- mide are agents with anti-inflammatory, immunomodulatory and anti- cancer activity. An excellent success rate has been shown for multiple myeloma in phase I/II clinical trials leading to Food and Drug Adminis- tration approval of lenalidomide. One mechanism by which these drugs could enhance anti-tumour immunity may be through enhanced dendritic cell (DC) function. Thalidomide, a compound structurally related to lena- lidomide and pomalidomide, is known to enhance DC function, and we have investigated whether its analogues, pomalidomide and lenalidomide, also have functional effects on DCs. We used mouse bone marrow-derived DCs treated with 5 or 10 lM pomalidomide, or lenalidomide from day 1 of culture. Treatment with IMiDimmunomodulatory compounds increased expression of Class I (H2-Kb), CD86, and pomalidomide also increased Class II (I-Ab) expression in bone marrow-derived DCs, as mea- sured by flow cytometry. Fluorescent bead uptake was increased by up to 45% when DCs were treated with 5 or 10 lM pomalidomide or lenalido- mide compared with non-treated DCs. Antigen presentation assays using DCs primed with ovalbumin, and syngeneic T cells from transgenic OTI and OTII mice (containing MHC restricted, ovalbumin-specific, T cells) showed that both pomalidomide and lenalidomide effectively increased CD8 + T-cell cross-priming (by up to 47%) and that pomalidomide alone was effective in increasing CD4 + T-cell priming (by 30%). Our observa-