title: 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.
abstract: 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-gamma, 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.
authors.affiliation: Research Unit, Saskatchewan Cancer Agency, Department of Oncology, College of Medicine, University of Saskatchewan, Saskatoon, Saskatchewan S7N 4H4, Canada.
authors.forename: Zhenmin
authors.initials: Z
authors.lastname: Ye
authors.forename: Chaoke
authors.initials: C
authors.lastname: Tang
authors.forename: Shulin
authors.initials: S
authors.lastname: Xu
authors.forename: Bei
authors.initials: B
authors.lastname: Zhang
authors.forename: Xueshu
authors.initials: X
authors.lastname: Zhang
authors.forename: Terence
authors.initials: T
authors.lastname: Moyana
authors.forename: Jicheng
authors.initials: J
authors.lastname: Yang
authors.forename: Jim
authors.initials: J
authors.lastname: Xiang
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002470:Cell Survival; D003602:Cytotoxicity, Immunologic; D007167:Immunotherapy; D051379:Mice; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000276:immunology* / Q000628:therapy*; D009374:Neoplasms, Experimental; D010047:Ovalbumin / Q000494:pharmacology; D010641:Phenotype; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
chemical_list: D010047:Ovalbumin