Fig. 6: CDK4/6i sensitizes LKB1-deficient tumors to anti-PD-1 therapy. | Nature Communications

Fig. 6: CDK4/6i sensitizes LKB1-deficient tumors to anti-PD-1 therapy.

From: CDK4/6 inhibition triggers ICAM1-driven immune response and sensitizes LKB1 mutant lung cancer to immunotherapy

Fig. 6

a, b C57BL/6 mice were subcutaneously inoculated with Lewis lung cancer cells with Lkb1 knockdown (LLC1-shLkb1) and administered different treatments (control immunoglobulin G (Vehicle), palbociclib or anti-PD-1 Ab, or co-treatment with palbociclib and anti-PD-1 Ab). Tumor size (a, n = 7 for vehicle, n = 7 for palbociclib, n = 6 for anti-PD-1 Ab, n = 6 for combination. Two-way ANOVA followed by Tukey’s multiple comparisons test was performed to compare the tumor growth curves in different treatment groups, **p = 0.0022, ***p = 0.0003, ****p < 0.0001) and survival (b, n = 9 for vehicle, n = 12 for palbociclib, n = 9 for anti-PD-1 Ab, n = 8 for combination. Log-rank test was used to analyze the survival data, ****p < 0.0001, ****p < 0.0001, ****p < 0.0001) in different treatment arms were monitored. c Tumor volumes were measured beginning on day 7 and continuing every two days until day 21. d, e LLC1-shLkb1-luc cell line was constructed and injected into the left chest of mice. Tumor formation was detected. Mice harboring lung tumors were administered different treatments (control immunoglobulin G (Vehicle), palbociclib or anti-PD-1 Ab, or co-treatment with palbociclib and anti-PD-1 Ab). Representative bioluminescent images (d) and quantification of results (e). n = 4 biologically independent mice examined over 1 independent experiment. One-way ANOVA followed by Tukey’s multiple comparisons test was performed. **p = 0.0097. f, g Genetically engineered Kras-driven mouse model with conditional deletion of Lkb1 (KL GEMM) Representative MRI images (f) of KL GEMM lung tumors prior to treatment and after two weeks of treatment. n = 3, n = 3, n = 3 and n = 4 in vehicle, anti-PD-1 Ab, palbociclib and co-treatment groups, respectively. The contours of lung tumors were sketched. Waterfall plot (g) shows tumor volume response to the treatment. Each column represents one mouse. One-way ANOVA followed by Tukey’s multiple comparisons test was performed. *p = 0.0312. (Results are presented as mean ± SEM. A mixed-effects model followed by Tukey’s multiple comparisons was performed to compare the tumor growth curves in different treatment groups. Log-rank test was used to analyze the survival data. ns, not significant; *p < 0.05; **p < 0.01; ***p < 0.001; ****p < 0.0001. Source data are provided as a Source Data file.).

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