Fig. 6

CDK7 inhibition stimulates antitumor immunity and sensitizes NSCLC to antiPD-1 therapy. a Photographs of tumors from the Lewis lung cancer model treated with the combination of THZ1 and antiPD-1 antibody (n = 7). b Tumor growth curves of mice from the Lewis lung cancer model. The dashed line represents a single mouse data in each group and the solid line represents the mean value in different groups. Error bars represent ± SEM (*P < 0.05; **P < 0.01). c Weights of tumors from mice in Lewis lung cancer model at the endpoint (*P < 0.05; ***P < 0.001). d Quantitation of PD-L1 level on tumor surfaces from the Lewis lung cancer model (***P < 0.001). e Quantification of percentages of CD45⁺ cells in tumors from the Lewis lung cancer model treated with the combination of THZ1 and antiPD-1 antibody (***P < 0.001). f Quantification of percentage of CD45⁺CD8⁺ cells in tumor from the Lewis lung cancer model treated with the combination of THZ1 and antiPD-1 antibody (n = 7) (**P < 0.01; ***P < 0.001). g The ratios of CD8⁺ T cell/CD45⁺ cell in tumors from the Lewis lung cancer model (***P < 0.001). h IFN-γ in the tumors from the Lewis lung cancer model was measured (***P < 0.001). The collected tumors were homogenized and detected by using Quantikine ELISA (R&D Systems). i C57BL/6 mice bearing Lewis tumor were treated with THZ1 or the combination of THZ1 and antiPD-1 with or without CD8⁺ T depletion by antibodies. The tumor burden of different groups was quantified by tumor weights at the endpoint (*P < 0.05; ***P < 0.001). j Kaplan-Meier survival analysis of patients with different risk scores by CDK7 protein level and tumor-infiltrating lymphocyte (TIL) scores in cohort II. High CDK7 protein level and low TIL scores were defined as two risk factors. Patients were stratified into three risk groups with different survival outcomes as follows: low-risk group without any risk factors = low CDK7 protein level and high TIL score (n = 64); medium risk group with only one risk factor (n = 126); high-risk group with two risk factors = high CDK7 protein level and low TIL score (n = 32) (*P < 0.05). k Kaplan-Meier survival analysis of patients with different risk scores by CDK7 protein level, MYC protein level, and TILs score in cohort II. High CDK7 protein level, high MYC protein level and low TIL score were defined as three risk factors. Patients were stratified into three risk groups with different survival outcomes as follows: low-risk group without any risk factors (n = 41); medium risk group with only one risk factor (n = 97); high-risk group with at least two risk factors (n = 84) (**P < 0.01). l Schematic illustration showing the CDK7-p38α-MYC axis dependent regulation of PD-L1 and the function of this signaling in NSCLC. The solid arrows represent strong processes; the dashed arrows represent very weak processes after CDK7 inhibition