Extended Data Fig. 8: The TNF axis is involved in immune-mediated colitis, as exacerbated by immune checkpoint blockade, in immune-deficient mice reconstituted with human PBMCs.
From: Prophylactic TNF blockade uncouples efficacy and toxicity in dual CTLA-4 and PD-1 immunotherapy
Fresh human PBMCs were injected intraperitoneally on day 0 into immunodeficient Rag2−/−Il2rg−/− mice. On days 0, 4, 7 and 10, mice were injected intraperitoneally with ipilimumab (200 µg) and nivolumab (200 µg), with or without etanercept (40 µg; given subcutaneously). As an antibody control, we used human polyclonal IgG. a, Normalized follow-up of body weight. Data are mean ± s.d. n = 4 biologically independent mice for all groups, except n = 5 for PBMCs + ICB + etanercept. P values were calculated using an extra sum-of-squares F test. b, Ultrasound assessments of intestinal wall thickness. Data are mean ± s.d. n = 4 biologically independent mice for PBMCs + IgG, n = 3 for PBMCs + ICB and n = 5 for PBMCs + ICB + etanercept. P values were calculated using a one-way ANOVA followed by Dunnett’s-test. c, Representative ultrasound images estimating colon wall thickness in the different experimental groups described in b. Red bars indicate intestinal wall thickness. Data are from a single experiment.
