title: High plasma levels of soluble programmed cell death ligand 1 are prognostic for reduced survival in advanced lung cancer.
abstract: 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.
  
  
  
  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.
  
  
  
  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).
  
  
  
  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.
authors.affiliation: 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.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Okuma
authors.affiliation: Department of Thoracic Oncology and Respiratory Medicine, Tokyo Metropolitan Cancer and Infectious diseases Center Komagome Hospital, Bunkyo, Tokyo 113-8677, Japan.
authors.forename: Yukio
authors.initials: Y
authors.lastname: Hosomi
authors.affiliation: Department of Respiratory Medicine, Kitasato University School of Medicine, Sagamihara, Kanagawa, 252-0375, Japan.
authors.forename: Yoshiro
authors.initials: Y
authors.lastname: Nakahara
authors.affiliation: Department of Thoracic Oncology and Respiratory Medicine, Tokyo Metropolitan Cancer and Infectious diseases Center Komagome Hospital, Bunkyo, Tokyo 113-8677, Japan.
authors.forename: Kageaki
authors.initials: K
authors.lastname: Watanabe
authors.affiliation: 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.
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Sagawa
authors.affiliation: 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.
authors.forename: Sadamu
authors.initials: S
authors.lastname: Homma
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D060890:B7-H1 Antigen / Q000097:blood* / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000097:blood; D005260:Female; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology*; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D013534:Survival; D019139:Tumor Escape / Q000276:immunology*
chemical_list: D060890:B7-H1 Antigen; D014408:Biomarkers, Tumor; C423236:CD274 protein, human
keywords: Immune evasion; Immune tolerance; Non-small cell lung cancer; Soluble programmed cell death ligand 1; Tumor escape