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. 2022 Nov 7;10(11):e004974. doi: 10.1136/jitc-2022-004974

Figure 6.

Figure 6

Prolonged survival in mice with combined Adar1 loss and DNMT inhibition is dependent on type I IFN signaling. (A) ID8 Trp53-/- shAdar1 knockdown tumor cells were grown in tissue culture dishes and then 5e6 cells were i.p. injected into C57Bl6 wild-type mice 1 day after the first injections of antibodies. THU/DNMTi treatment began around week 2. Survival curve for the following groups: shGFP Mock/isotype control group (n=5), shGFP Mock/anti-IFNAR1 group (n=5), shAdar1 THU/DNMTi/isotype control (n=7), shAdar1 THU/DNMTi/anti-IFNAR1 (n=5). Two mice from the shGFP Mock isotype control group were censored from the study because they had not developed tumors by the study end point (week 20). (B) Ascites (a buildup of fluid in the peritoneum) collected over time for mice in figure 6A. Ascites is a sign of advanced stage of disease and ascites volume is an indicator of tumor burden in this model. (C) Survival curve (n=5 per group). ID8 Trp5-/- shGFP (control) or shAdar1 knockdown tumor cells were grown in tissue culture dishes and then 5e6 cells were i.p. injected into mice. Mock or THU/DNMTi treatment began around week 2, and around week 6, mice began developing ascites (a buildup of fluid in the peritoneum). (D) Ascites (a buildup of fluid in the peritoneum) collected over time for mice in figure 6C. Ascites is a sign of advanced stage of disease and ascites volume is an indicator of tumor burden. (E) Ascites (a buildup of fluid in the peritoneum) collected over time for C57Bl6 wild-type mice that received shAdar1 tumors with THU/DNMTi treatment and either: (1) isotype control (n=10), (2) anti-IFNAR1 (n=10), (3) anti-CD8a (n=10), or (4) anti-NK1.1 (n=10) antibodies. ID8 Trp53-/- shAdar1 knockdown tumor cells were grown in tissue culture dishes and then 5e6 cells were i.p. injected into mice 1 day after the first injections of antibodies. THU/DNMTi treatment began around week 2. (F) Average volume of ascites (a buildup of fluid in the peritoneum) for C57Bl6 wild-type mice that received shAdar1 tumors with THU/DNMTi treatment and either: (1) isotype control (n=10), (2) anti-IFNAR1 (n=10), (3) anti-CD8a (n=10), or (4) anti-NK1.1 (n=10) antibodies. ID8 Trp53-/- shAdar1 knockdown tumor cells were grown in tissue culture dishes and then 5e6 cells were i.p. injected into mice 1 day after the first injections of antibodies. THU/DNMTi treatment began around week 2. *P<0.05; **p<0.01. DNMTi, DNA methyltransferase inhibitor; IFN, interferon; IFNAR1, interferon alpha and beta receptor 1; i.p., intraperitoneally; ns, not significant; THU, tetrahydrouridine.