IL-27受容体シグナルを欠損する活性化樹状細胞による腫瘍免疫増強

抄録

Interleukin (IL-) 27 is a member of the IL-12 cytokine family and is unique in that the cytokine has both immunostimulatory and immunosuppressive effects. While IL-27 is able to stimulate IFN-γ-production in T cells and NK cells, it suppresses activation of macrophages and dendritic cells. IL-27 also induces differentiation of IL-10-producing CD4⁺ T cell population, Tr1. Given the immunosuppressive effects of IL-27, IL-27-defficient or IL-27 receptor-deficient mice exhibited excessive, and often lethal, inflammation during infection with protozoa or mycobacterium. IL-27 was able to enhance anti-tumor activities of CD8⁺ T cells. IL-27 receptor-deficient dendritic cells exhibited enhanced antigen-presenting activities with augmented expression of co-stimulatory molecules and were able to induce higher tumor-killing activities by CD8⁺ T cells. Combination of IL-27 receptor-sufficient CD8⁺ T cells with IL-27 receptor-deficient activated dendritic cells efficiently led to high tumor-killing activity by CD8⁺ T cells. IL-27 thus is regarded as an immune checkpoint molecule to suppress excessive immune responses and is a potent target for development of novel immunosuppressive drug and/or for adjuvant discovery.