IL‐27 improves adoptive CD8<sup>+</sup> T cells’ antitumor activity via enhancing cell survival and memory T cell differentiation
Miao Ding, Fei Yi, Jianmin Zhu, Ji Ma, Guo‐Qing Zhu, Ni Zhen, Jiabei Zhu, Siwei Mao, Fenyong Sun, Feng Wang, Qiuhui Pan
Abstract
Abstract IL‐27 is an anti‐inflammatory cytokine that triggers enhanced antitumor immunity, particularly cytotoxic T lymphocyte responses. In the present study, we sought to develop IL‐27 into a therapeutic adjutant for adoptive T cell therapy using our well‐established models. We have found that IL‐27 directly improved the survival status and cytotoxicity of adoptive OT‐1 CD8 + T cells in vitro and in vivo. Meanwhile, IL‐27 treatment programs memory T cell differentiation in CD8 + T cells, characterized by upregulation of genes associated with T cell memory differentiation (T‐bet, Eomes, Blimp1, and Ly6C). Additionally, we engineered the adoptive OT‐1 CD8 + T cells to deliver IL‐27. In mice, the established tumors treated with OT‐1 CD8 + T‐IL‐27 were completely rejected, which demonstrated that IL‐27 delivered via tumor antigen–specific T cells enhances adoptive T cells’ cancer immunity. To our knowledge, this is the first application of CD8 + T cells as a vehicle to deliver IL‐27 to treat tumors. Thus, this study demonstrates IL‐27 is a feasible approach for enhancing CD8 + T cells’ antitumor immunity and can be used as a therapeutic adjutant for T cell adoptive transfer to treat cancer.