These findings indicate that lenalidomide can reverse CLL-induced immunosuppression through abrogation of the CXCL12–CXCR4–IL-10–STAT3 response in CLL cells and also prevention of T-cell suppression through inhibition of the IL-10-induced phosphorylation of Y705-STAT3. This evidence concerns the gene CXCR4 and B-cell chronic lymphocytic leukemia.