TY - JOUR
T1 - Local applications of GM-CSF induce the recruitment of immune cells in cervical low-grade squamous intraepithelial lesions
AU - Hubert, Pascale
AU - Doyen, Jean
AU - Capelle, Xavier
AU - Arafa, Mohammad
AU - Renoux, Virginie
AU - Bisig, Bettina
AU - Seidel, Laurence
AU - Evrard, Brigitte
AU - Bousarghin, Latifa
AU - Gerday, Colette
AU - Boniver, Jacques
AU - Foidart, Jean-Michel
AU - Delvenne, Philippe
AU - Jacobs, Nathalie
PY - 2010/8/1
Y1 - 2010/8/1
N2 - 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.
AB - 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.
KW - Adaptive Immunity/drug effects
KW - Administration, Topical
KW - Adult
KW - Antibodies, Viral/blood
KW - Antigen-Presenting Cells/drug effects
KW - Cell Line
KW - Cell Proliferation/drug effects
KW - Cervical Intraepithelial Neoplasia/drug therapy
KW - Female
KW - Granulocyte-Macrophage Colony-Stimulating Factor/administration & dosage
KW - Human papillomavirus 16/drug effects
KW - Humans
KW - Immunologic Factors/administration & dosage
KW - Keratinocytes/drug effects
KW - Lymphocyte Subsets/drug effects
KW - Lymphocytes, Tumor-Infiltrating/drug effects
KW - Middle Aged
KW - Natural Killer T-Cells/drug effects
KW - Neoplasms, Squamous Cell/drug therapy
KW - Papillomavirus Infections/blood
KW - T-Lymphocytes, Cytotoxic/drug effects
KW - Uterine Cervical Neoplasms/drug therapy
KW - Young Adult
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UR - http://www.scopus.com/inward/citedby.url?scp=77958086473&partnerID=8YFLogxK
U2 - 10.1111/j.1600-0897.2010.00834.x
DO - 10.1111/j.1600-0897.2010.00834.x
M3 - Article
C2 - 20367631
SN - 8755-8920
VL - 64
SP - 126
EP - 136
JO - American Journal of Reproductive Immunology and Microbiology
JF - American Journal of Reproductive Immunology and Microbiology
IS - 2
ER -