title: Bioactive suture: a novel immunotherapy for head and neck cancer.
abstract: OBJECTIVE
  We have proposed to characterize the mechanism through which bioactive surgical sutures generate a T(H)1 immune response and to define the immune-stimulating half-life of the sutures.
  
  
  METHODS
  Bioactive sutures of interferon gamma (IFNgamma), interleukin 2 (IL-2), anti-CD3/CD28, anti-CD3/CD28 + IL-2, or anti-CD3/CD28 + IFNgamma sutures were used to stimulate lymphocytes from normal donors and from head and neck cancer patients in vitro over a 24-day period. Cell supernatants were analyzed by ELISA, and T cells were phenotyped to characterize the immune response generated. Intracellular cytokine staining was performed to measure the expansion of flu-specific T cells. Electromobility shift assay and supershift assay were used to measure the intranuclear DNA binding activity of nuclear factor kappaB and its p65 subunit in T cells activated by sutures in the presence and absence of a proteasome inhibitor, MG-132.
  
  
  RESULTS
  Anti-CD3/CD28, anti-CD3/CD28 + IL-2, or anti-CD3/CD28 + IFNgamma generated a prolonged T(H)1 immune response for 18 days in vitro. Anti-CD3/CD28 expanded flu-specific T cells. Activated T cells demonstrated enhanced CD40 ligand (CD40L) expression within 72 hours of stimulation, which stimulated other cells to secrete IL-12. Stimulated T cells demonstrated increased intranuclear expression of nuclear factor-kappaB, which was blocked by MG-132, and also reduced CD40L and IL-12 expression.
  
  
  CONCLUSIONS
  This is the first report to demonstrate that bioactive surgical sutures can generate a prolonged T(H)1 immune response and expand flu-specific T cells. Bioactive sutures, which are primarily a T-cell stimulant, also stimulated other cells to secrete IL-12 and prolonged the immune response. Sutures may provide a novel in situ stimulating strategy for enhancing the immune system of cancer patients.
authors.affiliation: Department of Otolaryngology/Head & Neck Surgery, University of California Irvine College of Medicine, Orange, California 92868, USA. tshibuya@uci.edu
authors.forename: Terry Y
authors.initials: TY
authors.lastname: Shibuya
authors.forename: Sanghun
authors.initials: S
authors.lastname: Kim
authors.forename: Kevin
authors.initials: K
authors.lastname: Nguyen
authors.forename: Johnny
authors.initials: J
authors.lastname: Do
authors.forename: Christine E
authors.initials: CE
authors.lastname: McLaren
authors.forename: Kuo-Tung
authors.initials: KT
authors.lastname: Li
authors.forename: Wen-Pin
authors.initials: WP
authors.lastname: Chen
authors.forename: Parag
authors.initials: P
authors.lastname: Parikh
authors.forename: Ashish
authors.initials: A
authors.lastname: Wadhwa
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Zi
authors.forename: Vincent Y
authors.initials: VY
authors.lastname: Chen
authors.forename: Hau-Sin
authors.initials: HS
authors.lastname: Wong
authors.forename: William B
authors.initials: WB
authors.lastname: Armstrong
authors.forename: George H
authors.initials: GH
authors.lastname: Yoo
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001672:Biocompatible Materials; D016207:Cytokines / Q000008:administration & dosage* / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006258:Head and Neck Neoplasms / Q000276:immunology* / Q000628:therapy*; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D013536:Suture Techniques; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D001672:Biocompatible Materials; D016207:Cytokines