Xue Han1,2,3, Yang-Kui Gu1,2,3, Shao-Long Li1,2,3, Hao Chen1,2,4, Min-Shan Chen1,2,5, Qing-Qing Cai1,2,6, Han-Xia Deng1,2,3, Meng-Xuan Zuo7,8,9, Jin-Hua Huang10,11,12. 1. State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Guangzhou, 510060, People's Republic of China. 2. Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, People's Republic of China. 3. Department of Minimally Invasive Interventional Radiology, Sun Yat-sen University Cancer Center, Guangzhou, 510060, Guangdong, People's Republic of China. 4. Department of Clinical Laboratory, Sun Yat-sen University Cancer Center, Guangzhou, 510060, Guangdong, People's Republic of China. 5. Department of Hepatobiliary Surgery, Sun Yat-sen University Cancer Center, Guangzhou, 510060, Guangdong, People's Republic of China. 6. Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, 510060, Guangdong, People's Republic of China. 7. State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Guangzhou, 510060, People's Republic of China. Zuomx@sysucc.org.cn. 8. Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, People's Republic of China. Zuomx@sysucc.org.cn. 9. Department of Minimally Invasive Interventional Radiology, Sun Yat-sen University Cancer Center, Guangzhou, 510060, Guangdong, People's Republic of China. Zuomx@sysucc.org.cn. 10. State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Guangzhou, 510060, People's Republic of China. huangjh@sysucc.org.cn. 11. Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, People's Republic of China. huangjh@sysucc.org.cn. 12. Department of Minimally Invasive Interventional Radiology, Sun Yat-sen University Cancer Center, Guangzhou, 510060, Guangdong, People's Republic of China. huangjh@sysucc.org.cn.
Abstract
PURPOSE: Anti-programmed cell death-1 (PD-1)/programmed cell death-ligand 1 (PD-L1) therapy has shown promise in tumor immunotherapy. Our objectives were to measure pre-treatment serum-soluble PD-L1 (sPD-L1) levels and to assess the relationships between sPD-L1 levels and clinical characteristics, prognosis, and tumor tissue PD-L1 expression in patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). METHODS: Pre-treatment serum sPD-L1 levels were measured with an enzyme-linked immunosorbent assay (ELISA) in 81 patients with HBV-related HCC and compared to those in 49 healthy controls. The association between serum sPD-L1 levels and prognosis was assessed using survival analysis. The correlation between paired serum sPD-L1 levels and tumor PD-L1 expression (in resected tissue homogenates) was assessed in a separate group of 20 patients with HBV-related HCC. RESULTS: Median sPD-L1 concentration in patients with HBV-related HCC was 5.129 (range 0.140-12.391) ng/mL and in healthy controls was 0.836 (range 0.105-2.168) ng/mL (p < 0.001). On multivariate analysis, sPD-L1 levels were significant independent predictors of disease-free survival (hazard ratio [HR] 3.503; 95% confidence interval [CI], 1.559-7.871; p = 0.002) and overall survival (HR 3.399; 95% CI 1.308-8.831; p = 0.012). Positive correlation (r = 0.527, p = 0.017) between serum sPD-L1 and tumor PD-L1 expression was observed. Tumor expression of PD-L1 was significantly higher in those with serum sPD-L1 concentrations above vs. below the median level of 5.471 ng/ml (p = 0.012). CONCLUSIONS: In patients with HBV-related HCC, serum sPD-L1 concentrations were elevated, and positively correlated with tumor PD-L1 expression. Lower pre-treatment serum sPD-L1 levels were predictors of more favorable disease-free and overall survival. Serum sPD-L1 testing has a potential role in HBV-related HCC disease assessment, systemic therapy choices and survival prediction.
PURPOSE: Anti-programmed cell death-1 (PD-1)/programmed cell death-ligand 1 (PD-L1) therapy has shown promise in tumor immunotherapy. Our objectives were to measure pre-treatment serum-soluble PD-L1 (sPD-L1) levels and to assess the relationships between sPD-L1 levels and clinical characteristics, prognosis, and tumor tissue PD-L1 expression in patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). METHODS: Pre-treatment serum sPD-L1 levels were measured with an enzyme-linked immunosorbent assay (ELISA) in 81 patients with HBV-related HCC and compared to those in 49 healthy controls. The association between serum sPD-L1 levels and prognosis was assessed using survival analysis. The correlation between paired serum sPD-L1 levels and tumorPD-L1 expression (in resected tissue homogenates) was assessed in a separate group of 20 patients with HBV-related HCC. RESULTS: Median sPD-L1 concentration in patients with HBV-related HCC was 5.129 (range 0.140-12.391) ng/mL and in healthy controls was 0.836 (range 0.105-2.168) ng/mL (p < 0.001). On multivariate analysis, sPD-L1 levels were significant independent predictors of disease-free survival (hazard ratio [HR] 3.503; 95% confidence interval [CI], 1.559-7.871; p = 0.002) and overall survival (HR 3.399; 95% CI 1.308-8.831; p = 0.012). Positive correlation (r = 0.527, p = 0.017) between serum sPD-L1 and tumorPD-L1 expression was observed. Tumor expression of PD-L1 was significantly higher in those with serum sPD-L1 concentrations above vs. below the median level of 5.471 ng/ml (p = 0.012). CONCLUSIONS: In patients with HBV-related HCC, serum sPD-L1 concentrations were elevated, and positively correlated with tumorPD-L1 expression. Lower pre-treatment serum sPD-L1 levels were predictors of more favorable disease-free and overall survival. Serum sPD-L1 testing has a potential role in HBV-related HCC disease assessment, systemic therapy choices and survival prediction.
Authors: Lorena Incorvaia; Daniele Fanale; Giuseppe Badalamenti; Camillo Porta; Daniel Olive; Ida De Luca; Chiara Brando; Mimma Rizzo; Carlo Messina; Mattia Rediti; Antonio Russo; Viviana Bazan; Juan Lucio Iovanna Journal: Oncoimmunology Date: 2020-10-27 Impact factor: 8.110