ASSESSMENT OF CYTOTOXIC T-LYMPHOCYTE PHENOTYPE USING THE SPECIFIC MARKERS GRANZYME-B AND TIA-1 IN CERVICAL NEOPLASTIC LESIONS

Cervical carcinomas are closely associated with high-risk human papill omavirus (HPV) types and are preceded by cervical intraepithelial neop lasia (GIN). Most CIN lesions regress spontaneously and will not evolv e to invasive carcinoma. The cellular immune system mediated by cytoto xic T lymphocytes (CTLs) and natural killer (NK) cells are thought to play an important role in the ultimate decline of CIN lesions. Althoug h TIA-1 is constitutively expressed in the majority of circulating T c ells and defines a subpopulation of CD8(+) T cells with cytotoxic pote ntial, granzyme B is only expressed in CTLs upon activation. In the pr esent study we have evaluated the expression of these proteins by lymp hocytes present in 24 randomly chosen CIN lesions with increasing degr ee of atypia and in 14 cervical squamous cell carcinomas. As major his tocompatibility complex (MHC) class I expression is frequently down-re gulated in HPV-induced lesions, thus possibly frustrating tumour cell recognition by infiltrating CTLs, these lesions were also analysed for MHC class I expression. The results indicated that in most CIN lesion s only a minority of CTLs are activated, whereas in some carcinomas a massive infiltration of activated, i.e. granzyme B-positive, CTLs were observed. The percentage of activated CTLs was not related to express ion of MHC class I on neoplastic cells. These results suggest that in some carcinomas proper activation of CTLs occurs but that most likely local factors or immunoselection of resistant neoplastic cells inhibit a proper response of CTLs to these neoplastic cells.