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


METHODS
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.


CONCLUSIONS
These encouraging results obtained from a limited number of subjects justify further study on the therapeutic effect of APC in cervical (pre)neoplastic lesions.
Hubert
Pascale
P
Department of Pathology, GIGA-CANCER/GIGA-I3, University of Liège, B23 CHU Sart-Tilman, Liège, Belgium.
Doyen
Jean
J
Capelle
Xavier
X
Arafa
Mohammad
M
Renoux
Virginie
V
Bisig
Bettina
B
Seidel
Laurence
L
Evrard
Brigitte
B
Bousarghin
Latifa
L
Gerday
Colette
C
Boniver
Jacques
J
Foidart
Jean-Michel
JM
Delvenne
Philippe
P
Jacobs
Nathalie
N
D056704:Adaptive Immunity / Q000187:drug effects; D000287:Administration, Topical; D000328:Adult; D000914:Antibodies, Viral / Q000097:blood; D000938:Antigen-Presenting Cells / Q000187:drug effects / Q000276:immunology; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology*; D052162:Human papillomavirus 16 / Q000187:drug effects / Q000276:immunology / Q000302:isolation & purification; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology; D015603:Keratinocytes / Q000187:drug effects; D016131:Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology; D016246:Lymphocytes, Tumor-Infiltrating / Q000187:drug effects* / Q000276:immunology; D008875:Middle Aged; D055611:Natural Killer T-Cells / Q000187:drug effects / Q000276:immunology; D018307:Neoplasms, Squamous Cell / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology / Q000821:virology; D030361:Papillomavirus Infections / Q000097:blood / Q000150:complications / Q000276:immunology* / Q000821:virology; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000276:immunology; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology / Q000821:virology; D055815:Young Adult; D002578:Uterine Cervical Dysplasia / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology / Q000821:virology
D000914:Antibodies, Viral; D007155:Immunologic Factors; D016178:Granulocyte-Macrophage Colony-Stimulating Factor