Type 1 CD8+ T Cells are Superior to Type 2 CD8+ T Cells in Tumor Immunotherapy due to Their Efficient Cytotoxicity,Prolonged Survival and Type 1 Immune Modulation

摘要

CD8+ cytotoxic T（Tc） cells play a crucial role in host immune responses to cancer,and in this context,adoptive CD8+ Tc cell therapy has been studied in numerous animal tumor models. Its antitumor efficacy is,to a large extent,determined by the ability of Tc cells to survive and infiltrate tumors. In clinical trials,such in vitro-activated T cells often die within hours to days,and this greatly limits their therapeutic efficacy. CD8+ Tc cells fall into two subpopulations based upon their differential cytokine secretion. In this study,we in vitro generated that ovalbumin（OVA） -pulsed dendritic cell（DCOVA） -activated CD8+ type 1 Tc（Tc1） cells secreting IFN-γ,and CD8+ type 2 Tc（Tc2） cells secreting IL-4,IL-5 and IL-10,which were derived from OVA-specific T cell receptor（TCR） transgenic OT I mice. We then systemically investigated the in vitro and in vivo effector function and survival of Tc1 and Tc2 cells,and then assessed their survival kinetics after adoptively transferred into C57BL/6 mice,respectively. We demonstrated that,when compared to CD8+ Tc2,Tc1 cells were significantly more effective in perforin-mediated cytotoxicity to tumor cells,had a significantly higher capacity for in vivo survival after the adoptive T cell transfer,and had a significantly stronger therapeutic effect on eradication of well-established tumors expressing OVA in animal models. In addition,CD8+ Tc1 and Tc2 cells skewed the phenotype of CD4+ T cells toward Th1 and Th2 type,respectively. Therefore,the information regarding the differential effector function,survival and immune modulation of CD8+ Tc1 and Tc2 cells may provide useful information when preparing in vitro DC-activated CD8+ T cells for adoptive T cell therapy of cancer.