Interferon-γ Enhances Susceptibility of Cervical Cancer Cells to Lysis by Tumor-Specific Cytotoxic T Cells

• Published in: Gynecologic oncology 1997-05, Vol.65 (2), p.265-272
• Main Authors: Street, Daron, Kaufmann, Andreas M., Vaughan, Andrew, Fisher, Susan G., Hunter, Michael, Schreckenberger, Carola, Potkul, Ronald K., Gissmann, Lutz, Qiao, Liang
• Format: Article
• Language: English
• Subjects: B7-1 Antigen - biosynthesis; B7-1 Antigen - immunology; Biological and medical sciences; CD58 Antigens - biosynthesis; CD58 Antigens - immunology; Female; Female genital diseases; Gene Expression Regulation, Neoplastic; Gynecology. Andrology. Obstetrics; Humans; Intercellular Adhesion Molecule-1 - biosynthesis; Intercellular Adhesion Molecule-1 - immunology; Interferon-gamma - therapeutic use; Major Histocompatibility Complex - genetics; Major Histocompatibility Complex - immunology; Medical sciences; T-Lymphocytes, Cytotoxic - immunology; Tumor Cells, Cultured; Tumors; Up-Regulation; Uterine Cervical Neoplasms - immunology; Uterine Cervical Neoplasms - pathology; Uterine Cervical Neoplasms - therapy
• ISSN: 0090-8258; 1095-6859
• DOI: 10.1006/gyno.1997.4667

Recently we have demonstrated that tumor-specific cytotoxic T lymphocytes (CTLs) can be activated by cervical carcinoma cells expressing the costimulatory molecule CD80, which may be used as a therapeutic vaccine for patients with cervical cancer. For activated CTLs to be effective, appropriate amounts of MHC class I expression are required on target tumor cells. In this study, we found that some cervical carcinoma cells expressed only low levels of MHC class I and adhesion molecules such as CD54. We further demonstrated that tumor cells (CaSki and SiHa) expressing low levels of MHC class I were more resistant to lysis by specific CTLs than tumor cells (HeLa) expressing high levels of MHC class I. Treatment of CaSki or SiHa cells with interferon-γ resulted in an increased expression of MHC class I, MHC class II, and CD54. Expression of CD58 and CD80 was not up-regulated or induced. Treatment of the tumor cells with interferon-γ significantly enhanced the lysis of the tumor cells by specific CTLs which had been activated by the respective CD80-expressing tumor cells. The enhancement of cytolysis could be blocked by monoclonal antibodies to MHC class I and CD54, but not by that to MHC class II. Furthermore, we found that interferon-γ induced apoptosis in cervical carcinoma cells but not in tumor-specific CTLs.