Type 1 CD8~+ T Cells are Superior to Type 2 CD8~+ T Cells in Tumor Immunotherapy due to Their Effici

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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. 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 ovalbumin (OVA) -pulsed dendritic cell (DCOVA) -activated CD8 + type 1 Tc (Tc1) cells secreting IFN- γ, and CD8 + type 2 Tc -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 6 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. Thus, 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.
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