High plasma levels of soluble programmed cell death ligand 1 are prognostic for reduced survival in advanced lung cancer

• Published in: Lung cancer (Amsterdam, Netherlands) Vol. 104; pp. 1 - 6
• Main Authors: Okuma, Yusuke, Hosomi, Yukio, Nakahara, Yoshiro, Watanabe, Kageaki, Sagawa, Yukiko, Homma, Sadamu
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier B.V 01.02.2017
• Subjects: Adenocarcinoma - genetics; Adenocarcinoma - pathology; Adult; Aged; Aged, 80 and over; B7-H1 Antigen - blood; B7-H1 Antigen - metabolism; Biomarkers, Tumor - blood; Female; Hematology, Oncology and Palliative Medicine; Humans; Immune evasion; Immune tolerance; Immune Tolerance - immunology; Lung Neoplasms - drug therapy; Lung Neoplasms - metabolism; Lung Neoplasms - mortality; Lung Neoplasms - pathology; Male; Middle Aged; Non-small cell lung cancer; Prognosis; Prospective Studies; Pulmonary/Respiratory; Soluble programmed cell death ligand 1; Survival; Tumor escape; Tumor Escape - immunology; ALK; DLBCL; NSCLC; SQC; ECOG-PS; R-CHOP; CTLs; Immune evasion; mAb; RA; RCC; Immune tolerance; Non-small cell lung cancer; PD-L1; Tumor escape; Soluble programmed cell death ligand 1; PD-1; non-SQC; rituximabcyclophosphamide anthracycline vincristine and prednisone; cytotoxic T lymphocytes; diffuse large B-cell lymphoma; Eastern Cooperative Oncology Group Performance Status; soluble form of PD-L1; non-squamous cell lung cancernon; non-small cell lung cancer; anaplastic lymphoma kinase; squamous cell lung cancer; programmed cell death ligand-1; rheumatoid arthritis; programmed cell death-1; renal cell carcinoma; monoclonal antibody
• ISSN: 0169-5002; 1872-8332
• DOI: 10.1016/j.lungcan.2016.11.023

•PD-L1 in lung cancer is a key molecule for immune checkpoint mechanism.•The implication of soluble PD-L1 (sPD-L1) in lung cancer patients remains unknown.•High levels of sPD-L1 was associated with poor prognosis in advanced lung cancer.•SPD-L1 may be a useful biomarker for immune checkpoint therapy. 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