Abstract: Objective To explore the impact of anti-cancer drug Lenalidomide on the differentiation of monocytes to M2 polarized macrophages and the secretion of IL-10、VEGF and TGF-β1. Methods The peripheral blood mononuclear cells (PBMCs) were isolated by Ficoll-Hypaque density gradient centrifugation from peripheral blood of both lymphoma patients and healthy controls. Then PBMCs were co-cultured with HUT-78 lymphoma cells in Transwell 24-well plates. Anti-cancer drug Lenalidomide was added to the co-culture system. Expressions of the markers of TAMs (CD68 and CD163) were tested by flow cytometry. IL-10, VEGF and TGF-β1 level in the co-culture system were detected by ELISA. Results Treatment with Lenalidomide significantly decreased the proportion of CD68+, CD163+，CD68+CD163+ cells and the proportion of CD68+CD163+ / CD68+cells（P<0.05）. The degree of decline of CD68+CD163+ / CD68+cells was more significant in patients than that in healthy controls（P<0.05）. For patients, treatment with Lenalidomide significantly decreased the IL-10 and VEGF level in the co-culture system（P<0.01，P<0.05）. Conclusion Lenalidomide significantly inhibits the differentiation of monocytes to M2 polarized macrophages and down-regulate the secretion of IL-10 and VEGF in the co-culture system in patients group.

Key words: Key words Lenalidomide, Lymphoma, Tumor-associated macrophage