Fig. 5: Tumor-intrinsic mtRNA signaling contributes to CD8+-dependent anti-tumor immunity during CICD. | Nature Communications

Fig. 5: Tumor-intrinsic mtRNA signaling contributes to CD8+-dependent anti-tumor immunity during CICD.

From: Executioner caspases restrict mitochondrial RNA-driven Type I IFN induction during chemotherapy-induced apoptosis

Fig. 5: Tumor-intrinsic mtRNA signaling contributes to CD8+-dependent anti-tumor immunity during CICD.The alternative text for this image may have been generated using AI.

a B16 CASP3-/-7-/- cells were subjected to 5 days of ethidium bromide (EtBr) (100 ng/ml) or control-media pre-treatment before treatment with 1.5 µM doxorubicin for 24 h. RT-qPCR analysis of CXCL10 expression was performed. b B16 CASP3-/-7-/- cells were treated with 1.5 µM doxorubicin in the presence or absence of 5 µM IMT1B for 24 h before RT-qPCR analysis measuring CXCL10 and IFIT3 expression. Two-tailed unpaired t-test, p-values are included in the figure. Data are presented as mean ± SEM. c Western blot performed on B16 CASP3-/-7-/- cells with an additional CRISPR/Cas9 knockout against the specified protein after 24 h treatment with 1.5 µM of doxorubicin. Data are representative of three independent experiments (n = 3). d RT-qPCR analysis of CXCL10 expression in B16 CASP3-/-7-/- cells with or without IRF3 knockout following treatment of 1.5 µM doxorubicin for 24 h. e Tumor volume growth curves after subcutaneous injection of B16 wild-type control or CASP3-/-7-/- cells in the flanks of C57BL/6 mice treated with either doxorubicin (Dox) or saline. All treatment groups had a sample size of seven mice (n = 7) except Dox-treated CASP3-/-7-/- tumors, where six mice were used (n = 6). f Tumor volume growth curves after subcutaneous injection of B16 CASP3-/-7-/- cells with or without IRF3 knockout in the flanks of C57BL/6 mice treated with either doxorubicin (Dox) or saline. CASP3-/-7-/- tumors had a sample size of five mice (n = 5). CASP3-/-7-/- + IRF3-/- tumors had a sample size of six mice (n = 6). g Tumor volume growth curves after subcutaneous injection of B16 CASP3-/-7-/- cells with an additional knockout against STING or MAVS in the flanks of C57BL/6 mice treated with either doxorubicin (Dox) or saline. CASP3-/-7-/- tumors had a sample size of seven mice (n = 7). CASP3-/-7-/- + MAVS-/- and CASP3-/-7-/- + STING-/- tumors had a sample size of five mice (n = 5). h Tumor volume growth curves from mice after subcutaneous injection of B16 CASP3-/-7-/- cells in the flanks of C57BL/6 mice were treated with either doxorubicin (Dox) or saline in the presence of the indicated antibodies. These results are combined from two independent experiments. All saline treatment groups had a sample size of five mice (n = 5). All doxorubicin treatment groups had a sample size of six mice (n = 6). (i) Kaplan–Meier survival of mice in experiment (h). Statistical analysis by two-way ANOVA with Tukey’s multiple-comparison test in e–h and log-rank Mantel-Cox test in (i), p-values included in the figure. Data are presented as mean ± SEM; ns = not significant. a, d One-way ANOVA with Tukey’s multiple-comparison test was performed; p-values are included in the figure; ns = not significant. Data are presented as mean ± SEM. mRNA levels were normalized to DMSO-treated control B16 cells.

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