Figure 6. Combination therapy requires an intact loop of IL-7 and IFN-γ signalling pathways to reject MB49 tumours.

(a) Survival of WT and Ifngr1^−/− MB49 tumour-bearing mice untreated (UnTx) or treated with combo. (b) Survival of tumour-bearing mice pretreated with blocking antibody against IFN-γ (XMG1.2) and then treated with combination therapy. (c) Sublethally irradiated CD45.1 mice were adoptively transferred with WT, Ifngr1^−/− or Il7r^−/− total T cells, followed by MB49 tumour inoculation and combination therapy. Tumour growth kinetics is shown. (d) Rag-1^−/− mice were adoptively transferred with WT, Ifngr1^−/− or Il7r^−/− total T cells, followed by MB49 tumour inoculation and combination therapy. Tumour sizes on day 12 post-tumour inoculation are shown. (e) CD45.1 mice were treated as described above in c and mouse survivals are illustrated. (f,g) Isolated splenocytes from Il7r^−/− (f) and Ifngr1^−/− (g) tumour-bearing mice as described in Fig. 3 were analyzed for frequencies of CD4⁺CD44^hiCD122⁺ (T_CM) cells. Pooled results from five mice are depicted as bar graphs. (h,i) Isolated TILs from Ifngr1^−/− tumour-bearing mice treated with combination therapy were examined for IL-7Rα expression in CD4⁺ (H) or CD8⁺ (i). Data are means±s.e.m. of five mice in each group. NS, no statistical significance; *P<0.01; **P<0.01 by one-way ANOVA with Bonferroni's post hoc test (c,d), log-rank (Mantel–Cox) test (e) or two-tailed unpaired Student's t-test (f–i). Data are representative of two to three independent experiments.