CD4+ T cells play a crucial role for lenalidomide in vivo anti-tumor activity in murine multiple myeloma

// Liang Zhang 1, * , Enguang Bi 2, * , Sungyoul Hong 1, 3 , Jianfei Qian 1, 2 , Chengyun Zheng 4 , Michael Wang 1 , Qing Yi 1, 2 1 Department of Lymphoma/Myeloma, Division of Cancer Medicine, University of Texas MD Anderson Cancer Center, Houston, TX, United States 2 Deparment of Cancer Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, United States 3 Department of Pharmacy, College of Pharmacy, Seoul National University, Seoul, South Korea 4 Department of Hematology, Second Hospital of Shandong University, Jinan, PR China * These authors have contributed equally to this work Correspondence to: Qing Yi, e-mail: yiq@ccf.org Keywords: myeloma, 5TGM1, lenalidomide, immunomodulatory, CD4 + T cells Received: August 05, 2015      Accepted: September 21, 2015      Published: October 03, 2015 ABSTRACT Lenalidomide modulates the host immune response against myeloma via multiple actions. Although these effects have been elucidated in vitro , the central action of lenalidomide-mediated anti-myeloma immune response in vivo is not clear. To investigate its immune action in vivo , we selected the murine myeloma cell line 5TGM1, which is resistant to direct tumoricidal effects of lenalidomide in vitro and in immunodeficient mice, but sensitive to lenalidomide treatment in 5TGM1-bearing immunocompetent mice. Depletion of CD4 + T cells, but not NK cells, B cells, or CD8 + T cells, deprived lenalidomide of its therapeutic effects on 5TGM1-bearing immunocompetent mice. Lenalidomide significantly increased the numbers of IFN-γ-secreting CD4 + and CD8 + T cells but had no effects on NK cells and B cells in this mouse model. Lenalidomide slightly decreased the number of CD25 + Foxp3 + T cells but increased perforin expression in CD8 + T cells in vivo . Using this mouse model for investigation of anti-tumor immune action of lenalidomide, we demonstrated that lenalidomide facilitated a type-1 anti-tumor immune response in vivo . The CD4 + T cell subset may play a critical role in the lenalidomide-mediated anti-myeloma immune response in vivo .