Interferon-γ enhances susceptibility of cervical cancer cells to lysis by tumor-specific cytotoxic T cells

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.