Antitumor and antimetastatic activity of IL-23

Chia Hui Lo, Shan Chih Lee, Pin Yi Wu, Wen Yu Pan, Jui Su, Chao Wen Cheng, Steve R. Roffler, Bor Luen Chiang, Chun Nan Lee, Cheng Wen Wu, Mi Hua Tao

Research output: Contribution to journalArticlepeer-review

141 Citations (Scopus)

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 mm3, 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.

Original languageEnglish
Pages (from-to)600-607
Number of pages8
JournalJournal of Immunology
Volume171
Issue number2
Publication statusPublished - Jul 15 2003

ASJC Scopus subject areas

  • Immunology

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