Antitumor and antimetastatic activity of IL-23

被引:139
作者
Lo, CH
Lee, SC
Wu, PY
Pan, WY
Su, J
Cheng, CW
Roffler, SR
Chiang, BL
Lee, CN
Wu, CW
Tao, MH
机构
[1] Acad Sinica, Inst Biomed Sci, Taipei 115, Taiwan
[2] Natl Taiwan Univ, Grad Inst Med Technol, Taipei 10764, Taiwan
[3] Natl Taiwan Univ, Grad Inst Clin Med, Taipei 10764, Taiwan
[4] Natl Def Med Ctr, Grad Inst Life Sci, Taipei, Taiwan
[5] Natl Hlth Res Inst, Taipei, Taiwan
关键词
D O I
10.4049/jimmunol.171.2.600
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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.
引用
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页码:600 / 607
页数:8
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