Enhanced cross‐priming of naive CD 8 + T cells by dendritic cells treated by the IM i D s ® immunomodulatory compounds lenalidomide and pomalidomide

The IM i D s ® immunomodulatory compounds lenalidomide and pomalidomide 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 F ood and D rug A dministration 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 lenalidomide and pomalidomide, is known to enhance DC function, and we have investigated whether its analogues, pomalidomide and lenalidomide, also have functional effects on DC s. We used mouse bone marrow‐derived DC s treated with 5 or 10 μ m pomalidomide, or lenalidomide from day 1 of culture. Treatment with IM i D ® immunomodulatory compounds increased expression of C lass I ( H 2‐ K b), CD 86, and pomalidomide also increased C lass II (I‐ A b) expression in bone marrow‐derived DC s, as measured by flow cytometry. Fluorescent bead uptake was increased by up to 45% when DC s were treated with 5 or 10 μ m pomalidomide or lenalidomide compared with non‐treated DC s. Antigen presentation assays using DC s 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 CD 8 + T ‐cell cross‐priming (by up to 47%) and that pomalidomide alone was effective in increasing CD 4 + T ‐cell priming (by 30%). Our observations suggest that pomalidomide and lenalidomide enhance tumour antigen uptake by DC s with an increased efficacy of antigen presentation, indicating a possible use of these drugs in DC vaccine therapies.