BACKGROUND: This study aimed to investigate programmed death-ligand 1 tumor proportion score in predicting the safety and efficacy of PD-1/PD-L1 antibody-based therapy in treating patients with advanced non-small cell lung cancer (NSCLC) in a real-world setting. METHODS: This retrospective, multicenter, observational study enrolled adult patients who received PD-1/PD-L1 antibody-based therapy in China and met the following criteria: (1) had pathologically confirmed, unresectable stage III-IV NSCLC; (2) had a baseline PD-L1 tumor proportion score (TPS); and (3) had confirmed efficacy evaluation results after PD-1/PD-L1 treatment. Logistic regression, Kaplan-Meier analysis, and Cox regression were used to assess the progression-free survival (PFS), overall survival (OS), and immune-related adverse events (irAEs) as appropriate. RESULTS: A total of 409 patients, 65.0% ( n = 266) with a positive PD-L1 TPS (≥1%) and 32.8% ( n = 134) with PD-L1 TPS ≥50%, were included in this study. Cox regression confirmed that patients with a PD-L1 TPS ≥1% had significantly improved PFS (hazard ratio [HR] 0.747, 95% confidence interval [CI] 0.573-0.975, P = 0.032). A total of 160 (39.1%) patients experienced 206 irAEs, and 27 (6.6%) patients experienced 31 grade 3-5 irAEs. The organs most frequently associated with irAEs were the skin (52/409, 12.7%), thyroid (40/409, 9.8%), and lung (34/409, 8.3%). Multivariate logistic regression revealed that a PD-L1 TPS ≥1% (odds ratio [OR] 1.713, 95% CI 1.054-2.784, P = 0.030) was an independent risk factor for irAEs. Other risk factors for irAEs included pretreatment absolute lymphocyte count >2.5 × 10 9 /L (OR 3.772, 95% CI 1.377-10.329, P = 0.010) and pretreatment absolute eosinophil count >0.2 × 10 9 /L (OR 2.006, 95% CI 1.219-3.302, P = 0.006). Moreover, patients who developed irAEs demonstrated improved PFS (13.7 months vs. 8.4 months, P <0.001) and OS (28.0 months vs. 18.0 months, P = 0.007) compared with patients without irAEs. CONCLUSIONS A positive PD-L1 TPS (≥1%) was associated with improved PFS and an increased risk of irAEs in a real-world setting. The onset of irAEs was associated with improved PFS and OS in patients with advanced NSCLC receiving PD-1/PD-L1-based therapy.
Humans ; Carcinoma, Non-Small-Cell Lung/metabolism* ; Male ; Female ; Retrospective Studies ; Middle Aged ; Lung Neoplasms/metabolism* ; Aged ; B7-H1 Antigen/metabolism* ; Programmed Cell Death 1 Receptor/metabolism* ; Adult ; Aged, 80 and over ; Immune Checkpoint Inhibitors/therapeutic use*

Objective: To evaluate the effect of ticagrelor on plasma P-selectin (CD62P) concentration during acute kidney injury in septic rats. Methods: Thirty SPF healthy male Sprague-Dawley rats, aged 6-8 weeks, weighing 180-220 g, were divided into 3 groups(n=10 each)using a random number table method: sham operation group (group S), sepsis group (group Sep) and ticagrelor group (group T). Sepsis was induced by cecal ligation and puncture in anesthetized rats.The abdomen was opened after anesthesia induction and then closed after turning the intestines in group S. Ticagrelor 8.6 mg/kg was given through a gastric tube into stomach at 12 h after establishing the model in group T, while the equal volume of distilled water was given instead in S and Sep groups.Blood samples were collected from hearts at 24 h after establishing the model for determination of the concentrations of Scr and plasma CD62P.The rats were then sacrificed, and bilateral renal tissues were taken for examination of pathological changes and for determination of cell apoptosis by fluorescence microscopy after Annexin/V-FITC double staining was performed. Results: Compared with group S, the concentrations of Scr and plasma CD62P, renal Paller score and apoptosis rate of renal cells were significantly increased in Sep and T groups (P<0.05). Compared with group Sep, the concentrations of Scr and plasma CD62P, renal Paller score and apoptosis rate of renal cells were significantly decreased in group T (P<0.05). Conclusion The mechanism by which ticagrelor reduces acute kidney injury is related to decreasing plasma CD62P concentrations and inhibiting cell apoptosis in septic rats.

Objective To evaluate the effect of ticagrelor on plasma P-selectin(CD62P)concentra-tion during acute kidney injury in septic rats.Methods Thirty SPF healthy male Sprague-Dawley rats,aged 6-8 weeks,weighing 180-220 g,were divided into 3 groups(n＝10 each)using a random number table method: sham operation group(group S),sepsis group(group Sep)and ticagrelor group(group T).Sepsis was induced by cecal ligation and puncture in anesthetized rats.The abdomen was opened after anesthesia in-duction and then closed after turning the intestines in group S.Ticagrelor 8.6 mg/kg was given through a gas-tric tube into stomach at 12 h after establishing the model in group T,while the equal volume of distilled wa-ter was given instead in S and Sep groups.Blood samples were collected from hearts at 24 h after establishing the model for determination of the concentrations of Scr and plasma CD62P.The rats were then sacrificed,and bilateral renal tissues were taken for examination of pathological changes and for determination of cell ap-optosis by fluorescence microscopy after Annexin/V-FITC double staining was performed.Results Compared with group S,the concentrations of Scr and plasma CD62P,renal Paller score and apoptosis rate of renal cells were significantly increased in Sep and T groups(P＜0.05).Compared with group Sep,the concentra-tions of Scr and plasma CD62P,renal Paller score and apoptosis rate of renal cells were significantly de-creased in group T(P＜0.05).Conclusion The mechanism by which ticagrelor reduces acute kidney injury is related to decreasing plasma CD62P concentrations and inhibiting cell apoptosis in septic rats.