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
Yoon, S.J.; Lee, J.C.; Kang, J.O.; Lee, S.G.; Heo, D.S.
Anticancer Research 21(6a): 4031-4039
2001
ISSN/ISBN: 0250-7005 PMID: 11911288 Document Number: 530165
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.