Local applications of GM-CSF induce the recruitment of immune cells in cervical low-grade squamous intraepithelial lesions

Pascale Hubert, Jean Doyen, Xavier Capelle, Mohammad Arafa, Virginie Renoux, Bettina Bisig, Laurence Seidel, Brigitte Evrard, Latifa Bousarghin, Colette Gerday, Jacques Boniver, Jean-Michel Foidart, Philippe Delvenne, Nathalie Jacobs

Research output: Contribution to journalArticlepeer-review

9 Citations (Scopus)


PROBLEM: 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.

METHOD OF STUDY: 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.

CONCLUSION: These encouraging results obtained from a limited number of subjects justify further study on the therapeutic effect of APC in cervical (pre)neoplastic lesions.

Original languageEnglish
Pages (from-to)126-36
Number of pages11
JournalAmerican Journal of Reproductive Immunology and Microbiology
Issue number2
Publication statusPublished - Aug 1 2010


  • Adaptive Immunity/drug effects
  • Administration, Topical
  • Adult
  • Antibodies, Viral/blood
  • Antigen-Presenting Cells/drug effects
  • Cell Line
  • Cell Proliferation/drug effects
  • Cervical Intraepithelial Neoplasia/drug therapy
  • Female
  • Granulocyte-Macrophage Colony-Stimulating Factor/administration & dosage
  • Human papillomavirus 16/drug effects
  • Humans
  • Immunologic Factors/administration & dosage
  • Keratinocytes/drug effects
  • Lymphocyte Subsets/drug effects
  • Lymphocytes, Tumor-Infiltrating/drug effects
  • Middle Aged
  • Natural Killer T-Cells/drug effects
  • Neoplasms, Squamous Cell/drug therapy
  • Papillomavirus Infections/blood
  • T-Lymphocytes, Cytotoxic/drug effects
  • Uterine Cervical Neoplasms/drug therapy
  • Young Adult

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