Local Applications of GM-CSF Induce the Recruitment of Immune Cells in Cervical Low-Grade Squamous Intraepithelial Lesions

Citation Hubert P, Doyen J, Capelle X, Arafa M, Renoux V, Bisig B, Seidel L, Evrard B, Bousarghin L, Gerday C, Boniver J, Foidart J-M, Delvenne P, Jacobs N. Local applications of GM-CSF induce the recruitment of immune cells in cervical low-grade squamous intraepithelial lesions. Am J Reprod Immunol 2010; 64: 126–136 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-γ 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.