Figure 5 from CRISPR–Cas9 Screening Identifies KRAS-Induced COX2 as a Driver of Immunotherapy Resistance in Lung Cancer

Dual inhibition of EP2 and EP4 synergizes with ICB. A–C, M1/M2 macrophage ratio (A), percentage of Arg1⁺ CD11b⁺ TAMs (B), and percentage of CD69⁺ CD8⁺ T cells (C) in KPAR tumors treated twice daily for 7 days with 100 mg/kg TPST-1495. D, Kaplan–Meier survival of mice treated intraperitoneally with 200 μg anti-PD1 and/or twice daily oral gavage of 100 mg/kg TPST-1495 after orthotopic transplantation of KPAR cells, n = 8–12 mice per group. TPST-1495 treatment was initiated on day 7 and anti-PD1 began on day 10 and was administered twice weekly for a maximum of 3 weeks. Analysis of survival curves was carried out using the log-rank (Mantel–Cox) test. E, Heatmap showing hierarchical clustering of KPAR tumors treated for 7 days with TPST-1495 and/or anti-PD1 based on mRNA expression of antitumor immunity genes assessed by qPCR. F, mRNA expression by qPCR of immune-related genes in KPAR tumors treated as shown in E. Data are represented as mean ± SEM for A–C and F, n = 7–8 mice per group. Statistics were calculated using unpaired, two-tailed Student t test (A–C) or one-way ANOVA, FDR 0.05 (F). ns, not significant; *, P < 0.05; **, P < 0.01; ***, P < 0.001; ****, P < 0.0001.