Yusuke Okuma1, Yukio Hosomi2, Yoshiro Nakahara3, Kageaki Watanabe2, Yukiko Sagawa4, Sadamu Homma5. 1. Division of Oncology, Research Center for Medical Sciences, The Jikei University School of Medicine, Nishi-Shimbashi 3-25-8, Minato-ku, Tokyo 105-8461, Japan; Department of Thoracic Oncology and Respiratory Medicine, Tokyo Metropolitan Cancer and Infectious diseases Center Komagome Hospital, Bunkyo, Tokyo 113-8677, Japan. Electronic address: y-okuma@jikei.ac.jp. 2. Department of Thoracic Oncology and Respiratory Medicine, Tokyo Metropolitan Cancer and Infectious diseases Center Komagome Hospital, Bunkyo, Tokyo 113-8677, Japan. 3. Department of Respiratory Medicine, Kitasato University School of Medicine, Sagamihara, Kanagawa, 252-0375, Japan. 4. Division of Oncology, Research Center for Medical Sciences, The Jikei University School of Medicine, Nishi-Shimbashi 3-25-8, Minato-ku, Tokyo 105-8461, Japan. 5. Division of Oncology, Research Center for Medical Sciences, The Jikei University School of Medicine, Nishi-Shimbashi 3-25-8, Minato-ku, Tokyo 105-8461, Japan. Electronic address: sahya@jikei.ac.jp.
Abstract
OBJECTIVES: Programmed cell death-ligand 1 (PD-L1) expressed in tumor tissues is a key molecule for immune suppression, given its role in immune checkpoints. The significance and implication of soluble PD-L1 (sPD-L1) in the blood of lung cancer patients remain unknown. PATIENTS AND METHODS: Blood samples were prospectively collected from patients with advanced lung cancer, and the plasma sPD-L1 concentrations were measured by enzyme-linked immunosorbent assay. The correlations of the plasma sPD-L1 levels with clinico-pathological status, laboratory data, and survival of the patients were analyzed. RESULTS: Ninety-six patients with advanced lung cancer were analyzed, including 73 with adenocarcinoma, 12 with squamous cell carcinoma, and seven with small-cell lung cancer. Sixty-five were naïve to chemotherapy, and 20 had received two or more lines of chemotherapy. The mean plasma sPD-L1 concentration of all the patients was 6.95±2.90ng/ml (range 2.30-20.0ng/ml), and this value is significantly increased compared with that previously reported for normal subjects. No correlation of the plasma sPD-L1 level with histological subtypes, adenocarcinoma genetic status, smoking history, clinical stage or laboratory data was found. However, overall survival was significantly reduced in patients with high (≥7.32ng/ml) compared with low (<7.32ng/ml) plasma sPD-L1 levels (13.0 vs. 20.4 months, p=0.037). Multivariate analysis revealed that high sPD-L1 levels were significantly related to poor prognosis (hazard ratio 1.99, p=0.041). CONCLUSION: High plasma sPD-L1 levels were associated with poor prognosis in patients with advanced lung cancer, possibly associated with suppression of anti-tumor immunity. Clinical trial register and their clinical registration number: UMIN%000014760. Copyright Â
OBJECTIVES:Programmed cell death-ligand 1 (PD-L1) expressed in tumor tissues is a key molecule for immune suppression, given its role in immune checkpoints. The significance and implication of soluble PD-L1 (sPD-L1) in the blood of lung cancerpatients remain unknown. PATIENTS AND METHODS: Blood samples were prospectively collected from patients with advanced lung cancer, and the plasma sPD-L1 concentrations were measured by enzyme-linked immunosorbent assay. The correlations of the plasma sPD-L1 levels with clinico-pathological status, laboratory data, and survival of the patients were analyzed. RESULTS: Ninety-six patients with advanced lung cancer were analyzed, including 73 with adenocarcinoma, 12 with squamous cell carcinoma, and seven with small-cell lung cancer. Sixty-five were naïve to chemotherapy, and 20 had received two or more lines of chemotherapy. The mean plasma sPD-L1 concentration of all the patients was 6.95±2.90ng/ml (range 2.30-20.0ng/ml), and this value is significantly increased compared with that previously reported for normal subjects. No correlation of the plasma sPD-L1 level with histological subtypes, adenocarcinoma genetic status, smoking history, clinical stage or laboratory data was found. However, overall survival was significantly reduced in patients with high (≥7.32ng/ml) compared with low (<7.32ng/ml) plasma sPD-L1 levels (13.0 vs. 20.4 months, p=0.037). Multivariate analysis revealed that high sPD-L1 levels were significantly related to poor prognosis (hazard ratio 1.99, p=0.041). CONCLUSION: High plasma sPD-L1 levels were associated with poor prognosis in patients with advanced lung cancer, possibly associated with suppression of anti-tumor immunity. Clinical trial register and their clinical registration number: UMIN%000014760. Copyright Â
Authors: Marie-Nicole Theodoraki; Saigopalakrishna S Yerneni; Thomas K Hoffmann; William E Gooding; Theresa L Whiteside Journal: Clin Cancer Res Date: 2017-12-12 Impact factor: 12.531