Open AccessIL‐27 improves adoptive CD8 + T cells’ antitumor activity via enhancing cell survival and memory T cell differentiation
Author(s) -
Ding Miao,
Fei Yi,
Zhu Jianmin,
Ma Ji,
Zhu Guoqing,
Zhen Ni,
Zhu Jiabei,
Mao Siwei,
Sun Fenyong,
Wang Feng,
Pan Qiuhui
Publication year - 2022
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.15374
Subject(s) - cytotoxic t cell , adoptive cell transfer , cd8 , immunology , t cell , cancer research , interleukin 21 , biology , medicine , antigen , immune system , in vitro , biochemistry
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.