Antitumor and antimetastatic activity of IL-23
Antitumor and antimetastatic activity of IL-23
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DOI：
10.4049/jimmunol.171.2.600
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发表时间：
2003-07-15
影响因子：
4.4
通讯作者：
Tao, MH
中科院分区：
文献类型：
--
作者：
Lo, CH;Lee, SC;Tao, MH
最近发现的细胞因子IL-23的结构和T细胞刺激作用与IL-12的结构和T细胞刺激作用相似但不同。虽然IL-12的抗肿瘤活性已得到充分表征，但IL-23对肿瘤生长的影响尚不清楚。在这项研究中，小鼠CT 26结肠腺癌和B16 F1黑色素瘤细胞使用逆转录病毒载体进行工程改造，以释放单链IL-23（scIL-23），以评估其抗肿瘤活性。在BALB/c小鼠中，scIL-23转导的CT 26细胞逐渐生长，直到第26天达到521 +/- 333 mm的平均大小（3），然后大多数动物的肿瘤开始消退，最终肿瘤完全排斥率为70%。scIL-23转导还显著抑制CT 26和B16 F1肿瘤细胞的肺转移。此外，排斥scIL-23转导肿瘤的小鼠对随后的野生型肿瘤攻击产生了记忆反应。与表达scIL-12的CT 26细胞相比，scIL-23转导的肿瘤缺乏早期反应，但获得了相当的抗肿瘤和抗转移活性。这些结果表明，IL-23，像IL-12，提供了有效的保护，对恶性疾病，但它可能通过不同的抗肿瘤机制。作为确定这些抗肿瘤机制的第一步，在免疫功能低下的宿主和选择性耗竭各种淋巴细胞群的动物中进行肿瘤激发研究。结果表明，CD 8（+）T细胞，而不是CD 4（+）T细胞或NK细胞，是IL-23的抗肿瘤活性的关键。
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.