Modified immunoregulation associated with interferon-gamma treatment of rat glioma.
Little is known about modulation by cytokines of major histocompatibility complex (MHC) antigen expression on intracranial tumors in vivo. The ability of cytokines to up-regulate MHC class-1 (MHC-1) antigen expression was investigated first in vitro using three rat glioma cell lines. Immunohistochemistry showed that incubation with recombinant rat interferon-gamma (rrIFN-gamma) increased MHC-1 antigen expression in RG2, C6, and 9L cell lines. Flow cytometric analysis revealed different baseline levels of MHC-1 antigen expression in each line (RG2 lowest, C6 highest), and that these levels increased in all lines after stimulation with 100 U ml(-1) or more of rrIFN-gamma. The antitumor effect of rrIFN-gamma in vivo was evaluated by assessing survival of rats with implanted intracerebral RG2 gliomas after intracarotid infusion of rrIFN-gamma. A high dose of rrIFN-gamma (2.4 x 10(5) U kg(-1)) significantly increased the survival, compared to control (p < 0.02). Intracarotid pre-treatment with the bradykinin analogue RMP-7 did not further increase survival. Immunohistochemical staining of tumor sections after in vivo rrIFN-gamma, infusion showed no clear increase in MHC-1 antigen expression on tumor cells but increased staining for ED2 antigen within tumor tissue, presumably from perivascular cells with MHC class-2 antigen.
Oshiro
S
S
Maxine Dunitz Neurosurgical Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
Liu
Y
Y
Fukushima
T
T
Asotra
K
K
Black
K L
KL
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001920:Bradykinin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000276:immunology*; D002339:Carotid Arteries; D004359:Drug Therapy, Combination; D005260:Female; D005910:Glioma / Q000188:drug therapy* / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D007107:Immune System / Q000187:drug effects*; D007269:Injections, Intra-Arterial; D007371:Interferon-gamma / Q000627:therapeutic use*; D009368:Neoplasm Transplantation; D051381:Rats; D011916:Rats, Inbred F344; D011994:Recombinant Proteins / Q000627:therapeutic use; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D015395:Histocompatibility Antigens Class I; D011994:Recombinant Proteins; C089876:RMP 7; D007371:Interferon-gamma; D001920:Bradykinin