Extended Data Fig. 1: Mouse tumors harboring Pole/d1 functional mutations are sensitive to immunotherapy. | Nature Genetics

Extended Data Fig. 1: Mouse tumors harboring Pole/d1 functional mutations are sensitive to immunotherapy.

From: Functional landscapes of POLE and POLD1 mutations in checkpoint blockade-dependent antitumor immunity

Extended Data Fig. 1: Mouse tumors harboring Pole/d1 functional mutations are sensitive to immunotherapy.

a, Strategy to introduce PoleP286R into murine cell lines. b, Scheme of in vitro culture and WES (whole exome sequencing) of parental and PoleP286R mutant cell lines. c, Total SNV (single nucleotide variant) counts of the PoleP286R mutant and parental cell lines. P values by two-sided Student’s t-tests. d, B16F10 PoleP286R clone2 cell line with ICB therapies (N = 15 mice per group). P values (anti-CTLA4, P = 0.0003; anti-PD1, P = 0.0002; Combo, P = 0.0001). e, Survival analysis of mice bearing the B16F10 parental (anti-CTLA4, P = 0.14; anti-PD1, P = 0.13; Combo, P = 0.0003), the B16F10 PoleP286R (anti-CTLA4, P < 0.0001; anti-PD1, P < 0.0001; Combo, P < 0.0001) or the B16F10 PoleP286R clone2 tumors (anti-CTLA4, P < 0.0001; anti-PD1, P < 0.0001; Combo, P < 0.0001) after ICB (N = 15 mice per group). P values indicate log-rank test significance. f, CT-26- PoleP286R clone2 cell line with ICB therapies (N = 15 mice per group). P values (CTLA4 P = 1.1e-8, PD-1 P = 0.0015, Combo P = 3.2e-9). g, CT-26 PoleWT single cell clone1&2 tumors with ICB therapy (N = 15 mice per group). P values (Clone1 P = 0.023, Clone2 P = 0.053). h, Tumor inhibition rates of the CT-26 parental, PoleWT single clones and PoleP286R clone1 and clone2 tumors with anti-PD1 therapy at the last time point. (N = 15). Dots represent individual biological replicates. P values by two-sided Student’s t-tests. i, Growth curves of the B16F10 PoleV411L clone2 with anti-PD1 therapy (N = 15 mice per group, P = 0.0001). For all growth curves related panels (d,f,g,i), P values by two-sided Student’s t-tests at the end time points. For all panels, data are presented as mean values ± s.e.m. (n.s., no statistical significance, * P < 0.05, ** P < 0.01, *** P < 0.005, **** P < 0.0001). No multiple comparisons adjustment was performed.

Back to article page