A retroviral vector expressing human interferon gamma upregulates MHC antigen expression in human breast cancer and leukemia cell lines.
The use of cytokines to modify antigen expression on syngeneic murine tumor cells has led to immunization of the host from subsequent challenges with the parent tumor cell line. To determine whether this approach can be applied to human malignancies we introduced the human interferon gamma gene (IFN gamma) into the human breast cancer cell lines MDA-MB-435 and MDA-MB-231 using retroviral-mediated gene transfer. Retroviral transfer of the IFN gamma gene was associated with decreased growth, decreased tumor invasiveness, IFN gamma production, and upregulation of MHC antigens. While the MDA-MB-435 produced higher levels of IFN gamma than MDA-MB-231, MHC class I and class II antigens were upregulated in both cell lines. Introduction of this vector into the human leukemia cell line K562 led to increased expression of MHC class I antigens, but not class II. Our findings suggest that expression of interferon gamma in breast cancer cells may lead to increased recognition of breast cancer cells by the host immune system. Furthermore, these data suggest that further development of this approach to cancer immunotherapy is warranted.
Cornetta
K
K
Department of Medicine, Indiana University School of Medicine, Indianapolis 46202, USA.
Berebitsky
D
D
Behnia
M
M
Traycoff
C
C
Srour
E F
EF
Sledge
G W
GW
D000951:Antigens, Neoplasm / Q000096:biosynthesis* / Q000235:genetics; D001943:Breast Neoplasms / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D003094:Collagen; D004338:Drug Combinations; D015973:Gene Expression Regulation, Leukemic; D015972:Gene Expression Regulation, Neoplastic; D015316:Genetic Therapy; D005822:Genetic Vectors; D006680:HLA Antigens / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D007167:Immunotherapy; D007371:Interferon-gamma / Q000096:biosynthesis / Q000235:genetics* / Q000502:physiology; D007797:Laminin; D004915:Leukemia, Erythroblastic, Acute / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D009361:Neoplasm Invasiveness; D011509:Proteoglycans; D011994:Recombinant Proteins; D012190:Retroviridae; D014162:Transfection; D014407:Tumor Cells, Cultured
D000951:Antigens, Neoplasm; D004338:Drug Combinations; D006680:HLA Antigens; D007797:Laminin; D011509:Proteoglycans; D011994:Recombinant Proteins; C059485:matrigel; D007371:Interferon-gamma; D003094:Collagen