Anti-Tumor Immune Response Figure 5. CD8 T cell effector mechanisms. (A) Tumor growth and Kaplan-Meier survival curves in CY-treated IFN-c-deficient mice and control mice. Data shown are mean6SEM (n = 5) from one experiment (growth curve, left panel) or total data from two experiments (survival curve, right panel). Tumor cells were inoculated at day 0, treated with CY at day 9. * P,0.05 when CY in immunocompetent mice and IFN-c deficient mice is compared. (B) Tumor growth curves and Kaplan-Meier survival curves in CY-treated perforin-deficient and normal control mice. ns = not significant when CY in immuno-competent and perforin-deficient mice are compared. Tumor cells were inoculated at day 0 and treated with CY at day 8. ns, not significant. (C) Tumor growth and Kaplan-Meier survival curves after CY treatment in perforin/IFN-c double-deficient mice, compared to immunocompetent mice. Data shown are mean6SEM (n = 5) from one experiment (growth curve, left panel) or total data from two experiments (survival curve, right panel). Tumor cells were inoculated at day 0 and treated with CY at day 9. * P,0.05, *** P,0.001 when BALB/c + CY is compared with IFN-c/pfp-ko + CY. doi:10.1371/journal.pone.0006982.g005 antigens [30] and we hypothesized that CY-associated IFN responses might augment potential anti-tumor CD8 T cell responses. Indeed, this was the case in a MOPC-315 tumor model in which CY induced type-I IFN-dependent tumor regression [39]. However, CY-induced anti-tumor responses in our model are clearly less dependent on type-I IFNs, in contrast to the anti-tumor effects of poly-I:C and imiquimod in the same model [5,23]. This indicates that CY mobilizes anti-tumor CD8 T cells in a way that does not involve type-I IFN dependent activation and/or expansion [30,41]. CY depletes proliferating CD8 T cells, and, as we have recently shown, also CD4 T cells and foxp3+ regulatory CD4 T cells [18]. PLoS ONE | www.plosone.org 7 September 2009 | Volume 4 | Issue 9 | e6982