Fig. 7

Combination of IFN gene therapy with CTLA4 blockade or adoptively transferred OT-I T cells improves survival. a Survival curves of OVA-ALL-injected IFN (n = 14), CTRL (n = 14), IFN+αCTLA4 (n = 14), and CTRL+αCTLA4 (n = 15) mice, *p < 0.05, ***p < 0.001, Mantel–Haenszel test, adjusted by Bonferroni method. b Percentage of OVA-specific T cells within CD8+ T cells in the PB of mice from a. *p < 0.05, **p < 0.01, ****p < 0.0001, nonparametric rank-based method for longitudinal data in factorial experiments. c Clonality and similarity of the TCR-beta CDR repertoire of surviving mice (each arrow represents a mouse) from a before OVA-ALL injection (start of the arrow, T0) and 4 days after second tumor challenge (tip of the arrow, T2). d Survival curves of IFN + αCTLA4 (n = 10) and CTRL + αCTLA4 (n = 12) mice, *p < 0.05, Mantel–Haenszel test. e Survival curve of mice from d stratified based on their immune reactivity assessed by IFNγ-ELISPOT assay. Mice shown in red react against 2 or more surrogate tumor-specific antigens; mice shown in black react against 1 or no antigens. Note that reactivity against OVA and NGFR counts for 1 as their expression is co-regulated by a bidirectional promoter present within the lentiviral vector. f, g Experimental design (f) and OVA-ALL growth over time (g) (percentage in PB; mean ± SEM) in IFN (n = 7) or CTRL (n = 7) mice. h Absolute numbers (mean ± SEM) of OT-I T cells in BM and spleen of IFN (n = 7), CTRL (n = 7) and non tumor-bearing (C57Bl/6 no tumor, n = 3) mice 3 days upon OT-I adoptive transfer. *p < 0.05, **p < 0.01, Mann–Whitney. Each dot represents a mouse. i Experimental design (left) and survival curve (right) of OVA-ALL-injected CTRL (n = 12), IFN + OT-I (n = 9) and CTRL + OT-I (n = 10) mice. *p < 0.05, ****p < 0.0001 Mantel–Haenszel test, adjusted by Bonferroni test. j Absolute numbers (mean ± SEM) of adoptively transferred OT-I T cells in the PB over time of CTRL + OT-I and IFN + OT-I mice from i. Long-term surviving mice are shown in green. Each line represents a mouse. k Percentage (mean ± SEM) of Lag3 expression on OT-I T cells in the PB of mice from i. Long-term surviving mice are shown in green. Each line represents a mouse