title: Altered HLA expression by metastatic cervical carcinoma cells as a factor in impaired immune surveillance.
abstract: The altered expression of histocompatibility leukocyte antigens (HLA) in the development to cervical carcinoma suggests that tumor progression may be related to impaired recognition by host immune defense mechanisms. To investigate whether this phenomenon plays a role in the process of metastasis of cervical cancer, we analyzed and compared the HLA expression with the number of infiltrating immune cells in primary cervical carcinoma and related autologous metastases (n = 30) by staining serial paraffin and corresponding frozen sections with a panel of monoclonal antibodies. In 60% of the cervical metastases, compared to 21% of the primary tumors, a downregulation of monomorphic HLA class I antigens was observed, with frequent allele-specific alterations. In 50% the HLA class II expression was slightly increased on the metastatic tumor cells in comparison to the primary tumor. In addition, variability of alterations in HLA expression was observed between different metastases in the same patient. A minor infiltration of immune cells was present in cervical metastases compared to the primary tumors, especially in the HLA class I-downregulated metastases. Furthermore, loss of HLA class I expression on the metastatic tumor cells resulted in a significant decrease of tumor-infiltrating CD8+ T lymphocytes. These findings suggest that in cervical carcinoma loss of HLA class I expression plays a decisive role in the escape from immune surveillance leading to a greater metastatic potential of tumor cells.
authors.affiliation: Department of Pathology, University of Leiden, The Netherlands.
authors.forename: C G
authors.initials: CG
authors.lastname: Hilders
authors.forename: I M
authors.initials: IM
authors.lastname: Munoz
authors.forename: Y
authors.initials: Y
authors.lastname: Nooyen
authors.forename: G J
authors.initials: GJ
authors.lastname: Fleuren
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D017252:CD3 Complex / Q000032:analysis; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000276:immunology* / Q000556:secondary*; D018450:Disease Progression; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007108:Immune Tolerance; D007111:Immunity, Cellular / Q000276:immunology; D007150:Immunohistochemistry; D017493:Leukocyte Common Antigens / Q000032:analysis; D018655:Lymphocyte Count; D016246:Lymphocytes, Tumor-Infiltrating / Q000166:cytology / Q000276:immunology; D008264:Macrophages / Q000166:cytology / Q000276:immunology; D008875:Middle Aged; D015166:Monitoring, Immunologic; D012680:Sensitivity and Specificity; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology; D002583:Uterine Cervical Neoplasms / Q000235:genetics / Q000276:immunology* / Q000556:secondary*
chemical_list: D017252:CD3 Complex; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D017493:Leukocyte Common Antigens