Interferon-gamma 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-gamma 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-gamma 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-gamma induced apoptosis in cervical carcinoma cells but not in tumor-specific CTLs.
Street
D
D
Department of Obstetrics and Gynecology, Stritch School of Medicine, Loyola University Medical Center, Maywood, Illinois 60153, USA.
Kaufmann
A M
AM
Vaughan
A
A
Fisher
S G
SG
Hunter
M
M
Schreckenberger
C
C
Potkul
R K
RK
Gissmann
L
L
Qiao
L
L
D018122:B7-1 Antigen / Q000096:biosynthesis / Q000276:immunology; D018968:CD58 Antigens / Q000096:biosynthesis / Q000276:immunology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis / Q000276:immunology; D007371:Interferon-gamma / Q000627:therapeutic use*; D008285:Major Histocompatibility Complex / Q000235:genetics / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014407:Tumor Cells, Cultured; D015854:Up-Regulation; D002583:Uterine Cervical Neoplasms / Q000276:immunology* / Q000473:pathology / Q000628:therapy*
D018122:B7-1 Antigen; D018968:CD58 Antigens; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma