title: Functional investigation of Fas ligand expressions in human non-small cell lung cancer cells and its clinical implications.
abstract: BACKGROUND
  The purpose of this study is to investigate whether Fas ligand is functionally expressed in human lung cancer cells and to verify our hypothesis that specific inhibition of cancer-expressed FasL can improve the cellular immunity against cancer cells.
  
  
  METHODS
  The primary lung cancer cells (PLCCs) and autologous tumor-infiltrating lymphocytes (TILs) were separated from the surgical tissue samples. Western blot and immunofluorescence flow cytometry were used to detect the expressions of FasL. The FasL-specific small interfering (si)RNA was used to downregulate the expression of FasL, and a neutralizing mAb was used to block the ligation between FasL and Fas. Cancer cells and immune cells were alternatively selected as the effector cells or the target cells according to the different purposes. Cytotoxicity and apoptosis assays were used to detect the growth inhibition and apoptosis. The A549 cells and Jurkat T cells were co-cultured to study whether there is a counterattack against T cells. The PLCCs were co-cultured with autologous TILs to study whether specific blockage of cancer-expressed FasL can improve the TILs' cytotoxicity.
  
  
  RESULTS
  The FasL is functionally expressed in human lung cells and can facilitate cancer cells to counterattack immune cells. Activated immune cells are more vulnerable to counterattack. Targeting A549-expressed FasL by siRNA could significantly abrogate counterattack while blockade of PLCCs-expressed FasL by a neutralizing mAb could enhance TILs' cytotoxicity.
  
  
  CONCLUSIONS
  The improvement of cellular immunity against lung cancer depends on both activation and protection of immune cells. The specific inhibition of cancer-expressed FasL is effective in protecting immune cells, thus making FasL a new therapeutic target for cancer treatment.
authors.affiliation: Department of Thoracic Surgery, State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu City, China. yidanlin.lin@hotmail.com
authors.forename: Yidan
authors.initials: Y
authors.lastname: Lin
authors.forename: Lunxu
authors.initials: L
authors.lastname: Liu
authors.forename: Ting
authors.initials: T
authors.lastname: Zhang
authors.forename: Jin
authors.initials: J
authors.lastname: Liu
mesh_terms: D002289:Carcinoma, Non-Small-Cell Lung / Q000276:immunology* / Q000378:metabolism*; D053222:Fas Ligand Protein / Q000096:biosynthesis*; D006801:Humans; D007111:Immunity, Cellular; D008175:Lung Neoplasms / Q000276:immunology* / Q000378:metabolism*; D014407:Tumor Cells, Cultured
chemical_list: D053222:Fas Ligand Protein