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

Abstract

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.