Isolation and Characterization of Tumor Cell - Derived Immunoregulatory Factors

Lim, Jae Hyun; Kim, Hwa Jung; Jo, Eun Kyeong; Yoon, Wan Hee; Paik, Tae Hyun; Park, Jeong Kyu

Abstract

It has been known that the immunological functions against cancer cells were diminished, and these phenomena result from the inhibition of cell-mediated immunity by substance(s) secreted from cancer cells. It was also reported that the immunological functions decreased in patients with stomach cancer, which is the most frequent cnacer in Korean. However, the nature and function of the inhibitory factor(s) orignated from stomach cancer have not been identified. To elucidate effects of immuological inhibitory factor(s) secreted from cancer cells, SNU-1 (stomach cancer) and SW480 P109/R3P2 (colon cancer) were used in this study. Jurkat T cell line, an acute T cell leukemia, was pre-incubated with fractionated cancer cell culture supernatant for 3 days, then was stimulated with PMA, PWVanti-CD28 mAb or PMA/ionomycin for 8 hrs respectively. Fraction of SNU-1 (3 - 10 kDa) and above 10 kDa of SW480 P109/R3P2 inhibited the expression of IFN-r mRNA when Jurkat T cell was stimulated with PMA. However, there were no difference in IL-2 and IL-4 gene expression response to either PMA/anti-CD28 mAb or PMA/ionomycin. These results show that cancer cells secret some inhibitory factor(s) acting on the immune response, especially IFN-r gene expression of the Jurkat T cells response to PMA. Therefore, it suggests that the inhibitory factor(s) secreted from cancer cells influences on. the PKC-dependent pathway related to the signal transduction by PMA.