Loss of ICOSL expression in the progression to cervical carcinoma

Human papillomavirus (HPV)-related lesions contain types with benign
outcomes and those with a risk of progression to cancer. We addressed the
role of immune surveillance in 76 cervical biopsies (normal = 23, HPV+
benign = 16, HPV+ precancer = 37) by studying the infiltration of
cytotoxic T cells and the expression of the immune modulators PDL1, ICOSL,
and miR-155, and compared the data to 101 cervical squamous cell
carcinomas. In the normal cervix, ICOSL expression was restricted to the
endocervical epithelia, whereas neither miR-155 nor PDL1 was detected.
MiR-155 was up-regulated in both the benign (88%) and precancerous (92%)
HPV squamous intraepithelial lesions (SIL) and co-localized to cells in
the upper part of the lesion, that is, the area with productive viral
infection. Both PDL1 (95%) and ICOSL (89%) were only evident in the
precancerous SIL, and each localized to squamous cells in the basal aspect
that lacked replicating virus. In both microinvasive and invasive cervical
squamous cell cancer, miR-155 expression remained high (83%), as did PDL1
expression (80%), but ICOSL detection was reduced to 17%. Infiltration by
CD8+ T cells was intense in the invasive lesions, and these cells were
mostly inactive as determined by the lack of granzyme B co-localization.
It is concluded that miR-155 expression is a marker of HPV infection in
both benign and precancerous lesions, whereas approximately 10% of the
latter lesions that progress to cancer gain PDL1 and lose ICOSL
expression, which are important factors in avoiding immune surveillance.