Dendritic Cell Vaccination Combined with Pomalidomide and Dexamethasone Ameliorated Antitumor Immunity By Skewing Immuno-Suppressive Status Toward Immuno-Supportive Status in a Murine Myeloma Model

Pomalidomide (Pom) plus dexamethasone (Dex) could be considered one of the new treatment options in patients with relapsed and/or refractory multiple myeloma (MM). Recently, several diverse agents would be combined to improve the therapeutic efficacy. In this study, we investigated the preclinical efficacy of combined therapy with dendritic cells (DCs) and Pom-Dex in a murine myeloma model. After establishing myeloma-bearing mice, four treatment groups were designed to be a mimic protocol as like treatment in clinics as following: 1) PBS control, 2) DCs, 3) Pom + Dex, and 4) DCs + Pom + Dex. After vaccination, preclinical and in vitro immunological responses were evaluated. Treatment of DCs combined with Pom-Dex strongly inhibited tumor growth compared with other groups. In vitro immunological analyses revealed that these enhanced anti-tumor effects were closely associated with the decrease of immune-regulatory cell populations, such as regulatory T cells (Tregs), and the increase of effector immune cell populations, including activated CD4⁺ and CD8⁺ T cells, accompanied with the activation of cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells in the splenocytes from the treated mice. Moreover, the level of immunosuppressive cytokines, such as TGF-b and IL-10, was significantly reduced in tumor microenvironment. This study suggests that DC vaccination strongly enhances the anti-tumor immunity when combined with Pom and Dex, by skewing immuno-suppressive status toward immuno-supportive status in tumor microenvironment, in a murine myeloma model.