Characterising the local immune responses in cervical intraepithelial neoplasia: a cross-sectional and longitudinal analysis
Article first published online: 13 NOV 2008
© 2008 The Authors Journal compilation © RCOG 2008 BJOG An International Journal of Obstetrics and Gynaecology
BJOG: An International Journal of Obstetrics & Gynaecology
Volume 115, Issue 13, pages 1616–1622, December 2008
How to Cite
Woo, Y., Sterling, J., Damay, I., Coleman, N., Crawford, R., Van Der Burg, S. and Stanley, M. (2008), Characterising the local immune responses in cervical intraepithelial neoplasia: a cross-sectional and longitudinal analysis. BJOG: An International Journal of Obstetrics & Gynaecology, 115: 1616–1622. doi: 10.1111/j.1471-0528.2008.01936.x
- Issue published online: 13 NOV 2008
- Article first published online: 13 NOV 2008
- Accepted 3 August 2008.
- Human papillomavirus;
- local immune cell response
Introduction Immunological competence influences the progression of cervical intraepithelial neoplasia (CIN) to invasive cancer. Information on the local immunological changes during the natural course of CIN is central for the development of new therapies.
Objective This study defines the populations of tissue-infiltrating immune cells in a cross-sectional cohort of different grades of CIN and also in a longitudinal cohort of regressing, persistent and progressing low-grade (LG)-CIN.
Design A cohort of 125 women with LG cytological atypia was recruited, of which 64/125 (51%) women with LG-CIN were followed prospectively for 1 year. Paraffin-embedded entry and exit cervical biopsies were used for immunohistochemistry analysis (CD4, CD8, CD56, FOXP3, CD1a and granzyme B).
Results At recruitment, 74/125 (59%), 39/125 (31%) and 12/125 (10%) women referred with LG smears had histologically proven LG-CIN, high-grade (HG) and normal biopsies, respectively. Seventeen of 64 (24.6%) women with LG-CIN progressed to HG-CIN within 1 year. In both LG-CIN and HG-CIN, the predominant intraepithelial cell population were cytotoxic T cells, while CD4+ and FOXP3+ T cells predominated the stromal compartment. Women with LG-CIN who later on regressed displayed a significantly higher number of cytotoxic (granzyme B+) cells in their entry samples. In addition, the ratio between CD8+ cells and granzyme B+ cells was close to 1, suggesting that all infiltrating CD8+ T cells were highly active. In contrast, this ratio was three-fold lower in women, in whom the lesions persisted or progressed.
Conclusions This study suggests that the early infiltration of lesions by highly cytotoxic effector cells protects against progression.