Figure 2 : IFNAR1 expression by TSA cancer cells is required for optimal therapeutic response of mice treated with 8GyX3 and anti-CTLA4.

From: DNA exonuclease Trex1 regulates radiotherapy-induced tumour immunogenicity

Figure 2

(a) Upregulation of Ifnar1 expression measured by qRT-PCR 24 h after radiation in vitro in tetracycline-treated TSAshNS cells (black bars) is abrogated in TSAshIfnar1 cells (white bars) (Duplicate; *P<0.05; **P<0.005; ***P<0.0005: t-test; n=3). (b) pTRIPZ lentiviral vector with tetracycline-inducible shRNA and TurboRFP fluorescent protein (tRFP) expression, and microscopic image of tetracycline-treated TSAshNS cells (magnification= × 20). (cf) Mice bearing irradiated TSAshIfnar1 or TSAshNS tumours and TSAshNS tumours in the abscopal site were treated with tetracycline and 0Gy (TSAshNS=black; TSAshIfnar1=dashed line), 8GyX3 (TSAshNS=green; TSAshIfnar1=yellow), 8GyX3+anti-CTLA4 (TSAshNS=blue; TSAshIfnar1=red). (c) Growth of irradiated and abscopal tumours. Duplicate; *P<0.05; **P<0.005: comparison of irradiated tumour outgrowth; two-way ANOVA; n=7. (d) Survival. Numbers indicates fraction of tumour-free mice. Log-rank (Mantel–Cox) test for the survival experiment; n=7 (e) IFNγ production by tumour-draining lymph node (TDLN) cells in response to the CD8 T cell epitopes AH1A5 (full circles) or control peptide MCMV (open circles). Each symbol represents one animal. Horizontal lines indicate the mean of antigen-specific (solid lines) or control (dashed lines) IFNγ concentration. Duplicate; *P<0.05; **P<0.005; ***P<0.0005: t-test; n=3 (f) Individual tumour growth from (d) showing recurrence of all abscopal tumours in mice bearing irradiated TSAshIfnar1 tumours (red) while 3/7 mice with irradiated TSAshNS tumours (blue) remained tumour-free. All data are mean±s.e.m.