Fig. 7 | Nature Communications

Fig. 7

From: Interferon gene therapy reprograms the leukemia microenvironment inducing protective immunity to multiple tumor antigens

Fig. 7The alt text for this image may have been generated using AI.

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

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