436회 Cell-based anti-tumor immunotherapy

436회 

연사:  고 현 정, 강원대학교 약학대학 약학과

제목:  Cell-based anti-tumor immunotherapy

Abstract 

Of the available vaccine approaches, cellular vaccines using antigen-presenting cells (APC), such as dendritic cells (DC), are reliable at generating effective T-cell immunity. DCs are able to stimulate both CD4+ and CD8+ T cells by capturing, processing, and presenting antigens along with costimulatory signals. However, it is difficult to obtain sufficient number of DCs from cancer patient. For that reason, we investigated cellular vaccine using novel antigen presenting cells, including B cells and myeloid-derived suppressor cells (MDSCs). B cells are known for being poorly immunogenic and inducing T cell tolerance due to lack of costimulation but are abundant in patients. Previously, we have shown that activated NKT cells licensed B cells to generate long lasting cytotoxic anti-tumor immunity and induced innate anti-tumor immunity. Similarly, MDSCs, which accumulate in the spleen and bone marrow of tumor-bearing mice, were tested as APCs for a cellular vaccine. Although MDSCs have immunosuppressive properties, in vivo transferred MDSCs which present tumor antigen and natural killer T (NKT) cell ligand (alpha-galactosylceramide, αGalCer), significantly prolonged survival time in metastatic tumor-bearing mice in CD8+, NK, and NKT cells-dependent manner versus CD4+ T cells- and host DC-independent manner. αGalCer-loaded MDSCs did not suppress CD4+ and CD8+ T cells and allowed for the generation of antigen-specific CTL immunity, without increasing the generation of regulatory T cells. Furthermore, stimulation with activated NKT cells induced changes on MDSCs in phenotypical or maturation markers, including CD11b, CD11c, and CD86. As a result, these findings suggest that NKT cells facilitate the conversion of immunosuppressive MDSCs into immunogenic APCs, eliciting successful anti-tumor immunity and providing the basis for alternative cell-based vaccines. Taken together, both αGalCer- and antigen-loaded MDSCs could induce antigen specific immune responses and generate anti-tumor effects in vivo.