The Effects of Mesenchymal Stem Cells on Antimelanoma Immunity Depend on the Timing of Their Administration

Figure 5

The effects of MSCs on antimelanoma immunity depend on the timing of their administration. MSCs transplanted during the initial phase of melanoma growth exerted tumor-suppressive effects. Since these MSCs were exposed to the immunosuppressive microenvironment (established by IL-10 and TGF-β-producing tumor cells), they acquired inflammatory, MSC1 phenotype and induced expansion of cytotoxic NK cells and antitumorigenic CD8+CTLs, CD4+Th1, and Th17 lymphocytes, resulting in attenuated melanoma growth and progression. On the contrary, MSCs transplanted during the progressive stage of melanoma development were exposed to the high concentration of inflammatory cytokines (TNF-α and IFN-γ) and generated immunosuppressive, MSC2 phenotype. Accordingly, enhanced melanoma growth and reduced number of tumor-infiltrating antigen-presenting cells (macrophages and DCs), cytotoxic CTLs and NK cells, and antitumorigenic CD4+Th1 and Th17 lymphocytes were observed in melanoma-bearing mice which received MSCs during the progressive stage of tumor development.