title: The stimulatory activity of plasma in patients with advanced non-small cell lung cancer requires TLR-stimulating nucleic acid immunoglobulin complexes and discriminates responsiveness to chemotherapy.
abstract: BACKGROUND
  Therapeutic options for patients with non-small cell lung cancer (NSCLC) are often restricted to systemic chemotherapy. However, the molecular and cellular processes during chemotherapy of advanced NSCLC patients still remain unclear. Here we investigated the stimulatory activity of plasma in advanced NSCLC patients and its correlation with chemotherapy.
  
  
  METHODS
  Whole blood samples from advanced NSCLC patients were collected before the first, second, and third cycle of chemotherapy. Plasma was isolated following centrifugation of whole blood. PBMCs were isolated from whole-blood specimens by Ficoll-Hypaque density gradient centrifugation. Immune complexes (ICs) were isolated from NSCLC plasma using the IgG Purification Kit. qRT-PCR was used to detect a broad array of cytokines and chemokines.
  
  
  RESULTS
  The plasma in advanced NSCLC patients was endowed with stimulatory activity and capable of inducing proinflammatory cytokines. Both nucleic acids and immunoglobulin components were required for the stimulatory activity of NSCLC plasma. In consistent, TLR8 and TLR9 conferred the stimulatory activity of plasma in NSCLC patients. Of note, we revealed the decreased stimulatory activity of plasma in patients who responded to chemotherapy.
  
  
  CONCLUSIONS
  Our findings demonstrated that the plasma of advanced NSCLC patients required TLR-stimulating nucleic acid immunoglobulin complexes and could discriminate the responsiveness to chemotherapy, which might provide a novel mechanism by which the proinflammatory immune response was induced and a potential new biomarker for evaluating responsiveness to chemotherapy in NSCLC patients.
authors: Department of Scientific Research, East Hospital, Tongji University School of Medicine, Shanghai 200120, China ; Department of Preventive Medicine, East Hospital, Tongji University School of Medicine, Shanghai, China.
authors: Zengguang
authors: Z
authors: Xu
authors: Department of Oncology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China.
authors: Fengying
authors: F
authors: Wu
authors: Department of Respiratory Medicine, East Hospital, Tongji University School of Medicine, 150 Jimo Road, Pudong New Area, Shanghai 200120, China.
authors: Chunhong
authors: C
authors: Wang
authors: Department of Chest Surgery, The Bethune First Hospital of Jilin University, Changchun, China.
authors: Xiyu
authors: X
authors: Liu
authors: Department of Preventive Medicine, East Hospital, Tongji University School of Medicine, Shanghai, China.
authors: Baoli
authors: B
authors: Kang
authors: Department of Oncology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China.
authors: Shan
authors: S
authors: Shan
authors: Department of Respiratory Medicine, East Hospital, Tongji University School of Medicine, 150 Jimo Road, Pudong New Area, Shanghai 200120, China.
authors: Xia
authors: X
authors: Gu
authors: Department of Respiratory Medicine, East Hospital, Tongji University School of Medicine, 150 Jimo Road, Pudong New Area, Shanghai 200120, China.
authors: Kailing
authors: K
authors: Wang
authors: Department of Respiratory Medicine, East Hospital, Tongji University School of Medicine, 150 Jimo Road, Pudong New Area, Shanghai 200120, China.
authors: Tao
authors: T
authors: Ren
keywords: Chemotherapy; Immune complex; Non-small cell lung cancer; Toll-like receptor