Anti-tumor effect associated with down-regulation of MHC class 1 antigen after co-transfection of GM-CSF and IFN-gamma genes in CT26 tumor cells.
We previously reported that co-expression of GM-CSF and IFN-gamma genes in tumors induces a synergistic anti-tumor effect. Interestingly, we have used flow cytometry to identify two kinds of populations of CT26 cells that co-express GM-CSF and IFN-gamma genes: one population (CT26/G/I-down) that expresses very low levels of MHC class I and a second population (CT26/G/I-up) that expresses high levels of H-2Kd antigen. We have compared the anti-tumor effect between CT26/I-up and CT26/G/I-down cells. When wild-type (wt) CT26 cells were injected subcutaneously into Balb/c mice, tumor was formed 5-7 days after injection. However, when both CT26/G/I-up and CT26/G/I-down cells were injected, we did not identify any tumor. The protection' study showed that both CT26/G/I-up and CT26/G/I-down. cells could induce systemic immunity against secondary challenge with unmodified parental tumor cell. CT26/G/I-down cells showed normal expression of the heavy chain of MHC class I (HC), beta2-microglobulin (beta2m) and the TAP gene. Furthermore, in CT26/G/I-down cell, although the MHC molecules were detected normally in the cytoplasmic fraction, no message was detected in the membrane fraction. Pulse-chase experiments showed that class I antigen was normally synthesized like wt CT26 or CT26/G/I-up cells. Based on our results, non-MHC restricted immune effectors might play the major role in synergistic anti-tumor effects with co-expression of GM-CSF and IFN-gamma in CT26 tumor model.
Yoon
S J
SJ
Cancer Research Institute, Seoul National University Medical College, Korea.
Lee
J C
JC
Kang
J O
JO
Lee
S G
SG
Heo
D S
DS
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters; D000818:Animals; D003110:Colonic Neoplasms / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D015536:Down-Regulation; D005260:Female; D005822:Genetic Vectors / Q000235:genetics; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis / Q000235:genetics* / Q000494:pharmacology; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis / Q000235:genetics; D007143:Immunoglobulin Heavy Chains / Q000096:biosynthesis / Q000235:genetics; D007150:Immunohistochemistry; D007371:Interferon-gamma / Q000096:biosynthesis / Q000235:genetics* / Q000494:pharmacology; D008285:Major Histocompatibility Complex / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D011994:Recombinant Proteins; D012190:Retroviridae / Q000235:genetics; D014162:Transfection; D001613:beta 2-Microglobulin / Q000096:biosynthesis / Q000235:genetics
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters; D015395:Histocompatibility Antigens Class I; D007143:Immunoglobulin Heavy Chains; D011994:Recombinant Proteins; C073119:TAP1 protein, human; C486171:Tap1 protein, mouse; D001613:beta 2-Microglobulin; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor