a, T cell-dependent killing of ovalbumin-expressing
Adar1 p150/p110-null (red), p150-null (orange) and control
(grey) B16 tumour cells by OT-I transgenic T cells specific for an
ovalbumin-derived peptide in the context of MHC-I at decreasing E:T ratios
(1:20, 1:10 and 1:5). Data shown are representative of two independent
experiments with n = 3 replicates for each condition; mean
± s.e.m. b, Relative numbers of control,
Adar1 p150/p110-null, and Adar1 p150-null
B16 tumour cells stimulated with cytokines indicated compared with unstimulated
conditions (n = 3 for each condition; data are representative
of three independent experiments). c, Annexin V staining in
control, Adar1 p110/ p150-null and Adar1
p150-null tumours following stimulation with IFNβ, IFNγ or
IFNβ + IFNγ (n = 3 for each condition; data are
representative of three independent experiments). d, GSEA of gene
signatures in Adar1-null compared with control B16 tumour cells
after in vitro culture with IFNβ stimulation. n = 3 for
each condition; FDR calculated using GSEA. e, Enzyme-linked
immunosorbent assay (ELISA) for IFNβ in supernatant from control,
Adar1 p150/p110-null and Adar1 p150-null
B16 tumour cells after in vitro culture in unstimulated, IFNβ or
IFNγ conditions (n = 3 for each condition; data are
representative of three independent experiments). f, Tumour volume
following treatment with anti-PD-1 in vivo in genetic epistasis tumour models
that lack ADAR1 and components of IFN sensing pathways (n = 5
mice in each group, data representative of two independent experiments).
g, ELISA for IFNβ in supernatant from control and
Adar1 p150/p110-null B16 tumour cells following irradiation
in vitro (n = 3 for each condition; data representative of two
independent experiments). h, Tumour volume of control (grey) and
Adar1-null (red) B16 tumours following therapeutic
irradiation in vivo. n = 10 mice in each group; data are
representative of two independent experiments. b, c,
e, g, Bars represent mean; f, mean
± s.e.m. a–c, e, f,
h, Two-sided Student’s t-test;
*P < 0.05; **P < 0.01;
***P < 0.001, ****P <
0.0001; NS, not significant.