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. 2026 Oct 16;17:1910235. doi: 10.3389/fimmu.2026.1910235

Figure 3.

Five panels labeled A to E present experimental data on T cell responses to Navtemadlin. Panel A shows a bar and line graph depicting decreasing live cell numbers and viability with increasing drug concentrations. Panel B features a line graph comparing live cell counts for Tem and Tcm subsets, both declining at higher drug levels. Panel C consists of flow cytometry contour plots for 0 and 1 micromolar Nav, with corresponding scatter plots quantifying necrotic, apoptotic, and live Tcm and Tem cells. Panel D contains flow cytometry plots for IFN-γ and Granzyme B expression, and a bar graph showing increased double-positive cells at 1 micromolar Nav. Panel E includes a line graph of oxygen consumption rate over time and a bar graph showing elevated spare respiratory capacity at 1 micromolar Nav.

MDM2 mitigates apoptosis in central memory T cells and enhances metabolic fitness and polyfunctionality. Naïve human CD8+ T cells were activated with CD3/CD28/IL-2 for 5 days at different concentration of Navtemadlin as indicated. (A) Number of total live cells and viability and (B) number of live central and effector memory (right) were shown (n ≥ 3 biological replicates). (C) Representative Annexin V and PI flow plots for central (top) and effector (bottom) memory at 0μM and 1μM of Navtemadlin on day 5. Frequency of live (Annexin V- PI-), early apoptotic (Annexin V+ PI-), late apoptotic (Annexin V+ PI+), and necrotic (Annexin V- PI+) were plotted as seen in the bar plots (n = 3 biological replicates). (D) Representative flow plots of granzyme B (GzB) and interferon-gamma (IFN-γ) at 0μM and 1μM of Navtemadlin after 5-day culture (left). Frequency of polyfunctional CD8+ T cells were quantified (right) (n ≥ 3 biological replicates). (E) Oxygen consumption rate (OCR) and spare respiratory capacity (SRC) at 0μM and 1 μM of Navtemadlin (n ≥ 3 biological replicates). Oligomycin was injected after the 3rd measurement (approximately at minute 12), FCCP after the 6th measurement (approximately at minute 25), and rotenone and antimycin A after the 10th measurement (approximately at minute 40). Asterisks indicate statistical significance by one-way ANOVA followed by Dunnett’s multiple comparisons test: *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001. Bars represent mean and error bars indicate SEM. Colored asterisk indicate significant difference compared to 0 μM NAV control.