Ex vivo profiling of PD-1 blockade using MDOTS

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Presentation transcript:

Ex vivo profiling of PD-1 blockade using MDOTS Ex vivo profiling of PD-1 blockade using MDOTS. A, Schematic of MDOTS live/dead imaging workflow. Ex vivo profiling of PD-1 blockade using MDOTS. A, Schematic of MDOTS live/dead imaging workflow. B, MC38 implanted tumor volume (TV) following isotype control IgG (n = 10) or rat–anti-mouse anti–PD-1 antibody (n = 10) treatment (mean ± SEM, two-way ANOVA, Sidak multiple comparison test; **, P < 0.01; ****, P < 0.0001). C, Live (AO = green)/dead (PI = red) quantification of MC38 MDOTS day 0 (immediately after loading), day 3, and day 6 following IgG control or indicated anti–PD-1 antibody doses (n = 4, biological replicates, two-way ANOVA with Dunnett with multiple comparisons test; **, P < 0.01; ****, P < 0.0001). D, Live/dead analysis of MC38 spheroids lacking immune cells ± anti–PD-1 (n = 4, biological replicates). E, Live/dead analysis of B16F10 MDOTS ± anti–PD-1 (n = 3, biological replicates). F, Deconvolution fluorescence microscopy of MC38 and B16F10 MDOTS day 6 ± anti–PD-1 (representative images shown). G, Live/dead analysis of CT26 MDOTS ± anti–PD-1 (n = 3, biological replicates, two-way ANOVA with Dunnett with multiple comparisons test; ****, P < 0.0001). H, Live/dead analysis of CT26 MDOTS performed on day 6 following treatment with isotype IgG control (10 μg/mL) or anti–PD-1 (10 μg/mL) ± anti-CD8 (10 μg/mL; n = 6, biological replicates; two-way ANOVA with Tukey multiple comparisons test; ****, P < 0.0001; ns = not significant). I, CT26 TVs for responder (R1 + R2) and nonresponder (NR1 + NR2) BALB/c mice treated with anti–PD-1 (10 mg/kg twice weekly × 6 doses, starting at day 5) with time of tumor harvest for MDOTS preparation indicated (*). J, Live/dead analysis (day 6) of CT26 MDOTS from responder and nonresponder mice following ex vivo treatment with isotype IgG control (10 μg/mL) or anti–PD-1 (10 μg/mL; n = 3, biological replicates; two-way ANOVA with Tukey multiple comparisons test; ***, P < 0.001; ns = not significant). Russell W. Jenkins et al. Cancer Discov 2018;8:196-215 ©2018 by American Association for Cancer Research