Skip to main content
. 2023 May 26;9(21):eade4186. doi: 10.1126/sciadv.ade4186

Fig. 7. PD-L1 K162 hypermethylation is a predictive biomarker of PD-1/PD-L1 blockade resistance therapy.

Fig. 7.

(A to D) Ten NSCLC samples and its WCE were collected; measuring PD-L1 and PD-L1 k162 methylation level by IB analysis; investigating cytotoxicity of tumor-infiltrating CD8+ T cells in tumor specimens by flow cytometry analysis. Pearson’s correlation between PD-L1 K162me/PD-L1 ratio and the number/cytotoxicity of tumor-infiltrating CD8+ T cells was shown; n = 10. (E and F) Collecting 70 clinic samples from patients with NSCLC receiving anti–PD-1 treatment, IF assays measuring PD-L1, PD-L1 K162me, SETD7, and LSD2 expression level; Pearson’s correlation between PD-L1 K162me/PD-L1 ratio and SETD7 (E) or LSD2 (F) was shown; n = 70, P = 0.021 (E), P = 0.01 (F). (G) Kaplan-Meier survival analysis was shown. Patients were grouped by PD-L1 expression level; n = 33 (high), n = 33 (low), P = 0.9345. (H) Shown is the PD-L1 relative expression level of patients with anti–PD-1 treatment resistance or sensitivity; n = 45 (sensitivity), n = 22 (resistance), P = 0.0155. (I) Shown is the PD-L1 K162me/PD-L1 relative ratio of patients with anti–PD-1 treatment resistance or sensitivity; n = 45 (sensitivity), n = 22 (resistance), P < 0.0001. (J) Receiver operating characteristic curve analysis for the indicated parameters in patients receiving anti–PD-1 treatment. (K) Shown is the PD-L1 and PD-L1 K162me expression level of patients with NSCLC receiving anti–PD-1 treatment; red (sensitivity), black (resistance); the axes were separated by the Youden index. (L) Shown is the PD-L1 and PD-L1 K162me/PD-L1 expression level of patients with NSCLC receiving anti–PD-1 treatment; red (sensitivity), black (resistance); the axes were separated by the Youden index. (M) Kaplan-Meier survival analysis was shown; patients were grouped by the PD-L1 K162me/PD-L1 ratio; n = 33 (high), n = 33 (low), P = 0.0261. (N) Working model of SETD7-catalyzed LSD2-antagonized PD-L1 K162 methylation cross-talk with host antitumor immunity and anti-PD-(L)1 treatment prognosis. Error bars are means ± SD. Statistical significance was assessed using Student’s two-tailed t test.