Antitumor and Antimetastatic Activity of Il-23
Resource
JOURNAL OF IMMUNOLOGY v.171 n.2 pp.600-607
Journal
JOURNAL OF IMMUNOLOGY
Journal Volume
v.171
Journal Issue
n.2
Pages
600-607
Date Issued
2003
Date
2003
Author(s)
Lo, C.-H.
Lee, S.-C.
Wu, P.-Y.
Pan, W.-Y.
Su, J.
Cheng, C.-W.
Roffler, S. R.
Chiang, B.-L.
Lee, C.-N.
Wu, C.-W.
Tao, M.-H.
Abstract
The structure and T cell stimulatory effects of the recently discovered cytokine IL-23 are similar to, but distinct from , those of IL-12. Although the antitumor activities of IL-12 are well characterized, the effect of IL-23 on tumor growth is not known. In this study, murine CT26 colon adenocarcinoma and B16F1 melanoma cells were engineered using retroviral vectors to release single-chain IL-23 (scIL -23) to evaluate its antitumor activity. In BALB/c mice, scIL-23-transduced CT26 cells grew progressively until day 26 to an average size of 521 +/- 333 mm(3), then the tumors started to regress in most animals, resulting in a final 70% rate of complete tumor rejection. scIL-23 transduction also significantly suppressed lung metastases of CT26 and B16F1 tumor cells. In addition, mice that rejected scIL-23- transduced tumors developed a memory response against subsequent wild-type tumor challenge. Compared with scIL-12- expressing CT26 cells, scIL-23-transduced tumors lacked the early response , but achieved comparable antitumor and antimetastatic activity. These results demonstrated that IL- 23, like IL-12, provided effective protection against malignant diseases, but it probably acted by different antitumor mechanisms. As a first step in identifying these antitumor mechanisms, tumor challenge studies were performed in immunocompromised hosts and in animals selectively depleted of various lymphocyte populations. The results showed that CD8(+) T cells, but not CD4(+) T cells or NK cells, were crucial for the antitumor activity of IL-23.
Subjects
IFN-GAMMA PRODUCTION
TUMOR-REGRESSION
IMMUNE-RESPONSE
COLON- TUMOR
T-CELLS
INTERLEUKIN-12
Type
journal article