title: Local applications of GM-CSF induce the recruitment of immune cells in cervical low-grade squamous intraepithelial lesions.
abstract: OBJECTIVE
  Quantitative alterations of antigen-presenting cells (APC) in (pre)neoplastic lesions of the uterine cervix associated with human papillomavirus (HPV) infection suggest a diminished capacity to capture viral antigens and to induce a protective immune response.
  
  
  METHODS
  To test whether a cervical application of GM-CSF could restore an immune response against HPV in women with cervical low-grade squamous intraepithelial lesions (LSIL), we performed two clinical trials with 11 healthy women and 15 patients with LSIL.
  
  
  RESULTS
  GM-CSF applications were well tolerated in all enrolled women, and no difference in toxicity between the treated and placebo groups was observed during the follow-up (until 30 months). Interestingly, in the GM-CSF treated group, a significant increase of APC and cytotoxic T-lymphocyte infiltration was observed in the cervical biopsies with no change in regulatory T cell numbers. All the HPV16(+) patients exhibited an immune response against HPV16 after GM-CSF applications, as shown by NK and/or T cells producing IFN-gamma whereas no cellular immune response was observed before the treatment. Moreover, the anti-virus-like particles antibody titers also increased after the treatment.
  
  
  CONCLUSIONS
  These encouraging results obtained from a limited number of subjects justify further study on the therapeutic effect of APC in cervical (pre)neoplastic lesions.
authors.affiliation: Department of Pathology, GIGA-CANCER/GIGA-I3, University of Liège, B23 CHU Sart-Tilman, Liège, Belgium.
authors.forename: Pascale
authors.initials: P
authors.lastname: Hubert
authors.forename: Jean
authors.initials: J
authors.lastname: Doyen
authors.forename: Xavier
authors.initials: X
authors.lastname: Capelle
authors.forename: Mohammad
authors.initials: M
authors.lastname: Arafa
authors.forename: Virginie
authors.initials: V
authors.lastname: Renoux
authors.forename: Bettina
authors.initials: B
authors.lastname: Bisig
authors.forename: Laurence
authors.initials: L
authors.lastname: Seidel
authors.forename: Brigitte
authors.initials: B
authors.lastname: Evrard
authors.forename: Latifa
authors.initials: L
authors.lastname: Bousarghin
authors.forename: Colette
authors.initials: C
authors.lastname: Gerday
authors.forename: Jacques
authors.initials: J
authors.lastname: Boniver
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Foidart
authors.forename: Philippe
authors.initials: P
authors.lastname: Delvenne
authors.forename: Nathalie
authors.initials: N
authors.lastname: Jacobs
mesh_terms: D056704:Adaptive Immunity / Q000187:drug effects; D000287:Administration, Topical; D000328:Adult; D000914:Antibodies, Viral / Q000097:blood; D000938:Antigen-Presenting Cells / Q000187:drug effects / Q000276:immunology; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology*; D052162:Human papillomavirus 16 / Q000187:drug effects / Q000276:immunology / Q000302:isolation & purification; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology; D015603:Keratinocytes / Q000187:drug effects; D016131:Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology; D016246:Lymphocytes, Tumor-Infiltrating / Q000187:drug effects* / Q000276:immunology; D008875:Middle Aged; D055611:Natural Killer T-Cells / Q000187:drug effects / Q000276:immunology; D018307:Neoplasms, Squamous Cell / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology / Q000821:virology; D030361:Papillomavirus Infections / Q000097:blood / Q000150:complications / Q000276:immunology* / Q000821:virology; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000276:immunology; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology / Q000821:virology; D055815:Young Adult; D002578:Uterine Cervical Dysplasia / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology / Q000821:virology
chemical_list: D000914:Antibodies, Viral; D007155:Immunologic Factors; D016178:Granulocyte-Macrophage Colony-Stimulating Factor