Figure 10. Fas signaling controls T cell differentiation and influences adoptive immunotherapy efficacy.

(A) Tumor regression and (B) animal survival of mice bearing 10-day established s.c. B16 melanomas treated with 2.5 × 10⁵ T_N-derived pmel-1 cells primed alone, with lz-FasL (50 ng/ml), or with T_Mem in the presence of αFasL or IgG control. Viable cells were isolated using a density separation media before infusion. All treated mice received 6 Gy irradiation prior to cell infusion in addition to i.v. rVV-gp100 and 3 days of i.p. IL-2. Tumor treatment experiments performed with n = 5 mice/group. T_Mix, T_N cells primed with T_Mem cells in a 1:1 mixture. (C) Engraftment efficiency of Thy1.1⁺ T_N-derived pmel-1 cells (3 × 10⁵) primed alone or with lz-FasL 18 hours following i.v. adoptive transfer into nonirradiated Ly5.2⁺ hosts; n = 5 mice/group. (D) Correlation between the slope of tumor growth and CD62L expression at the time of cell transfer on T_N-derived pmel-1 cells primed alone with either lz-FasL (50 ng/ml), vehicle control, or with T_Mem and either αFasL or IgG. Pooled results from 2 independently performed experiments displayed using n = 4–10 mice per condition. Statistical comparisons performed using an unpaired 2-tailed Student’s t test or log-rank test for animal survival. *P < 0.05. Data shown are representative of 2 independent experiments with results displayed as mean ± SEM.