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.
|Number of pages||11|
|Journal||American Journal of Reproductive Immunology and Microbiology|
|Publication status||Published - Aug 1 2010|
- Adaptive Immunity/drug effects
- Administration, Topical
- Antibodies, Viral/blood
- Antigen-Presenting Cells/drug effects
- Cell Line
- Cell Proliferation/drug effects
- Cervical Intraepithelial Neoplasia/drug therapy
- Granulocyte-Macrophage Colony-Stimulating Factor/administration & dosage
- Human papillomavirus 16/drug effects
- 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