IL-28 elicits antitumor responses against murine fibrosarcoma
IL-28 elicits antitumor responses against murine fibrosarcoma
复制标题
DOI：
10.4049/jimmunol.178.8.5086
复制
发表时间：
2007-04-15
影响因子：
4.4
通讯作者：
Yamaya, Mutsuo
中科院分区：
文献类型：
--
作者：
Numasaki, Muneo;Tagawa, Masatoshi;Yamaya, Mutsuo
第28章最近描述了抗病毒细胞因子。在这项研究中，我们研究了IL-28对肿瘤生长的生物学效应，以评估其抗肿瘤活性。IL-28或IL-28基因的逆转录病毒转导到MCA 205细胞中不影响体外生长，而与对照相比，MCA 205 IL-28的体内生长被显著抑制沿着存活优势。当将分泌IL-28的MCA 205细胞的转移能力与对照进行比较时，IL-28的表达导致肺中转移形成的有效抑制。IL-28介导的肿瘤生长抑制在照射小鼠中大部分被消除，表明辐射敏感细胞，可能是免疫细胞，主要参与IL-28诱导的肿瘤生长抑制。体内细胞耗竭实验显示，多形核中性粒细胞、NK细胞和CD 8 T细胞，而不是CD 4 T细胞，在IL-28介导的体内肿瘤生长抑制中发挥同等作用。与这些发现相一致，将MCA 205 IL-28接种到小鼠中诱发脾细胞中IFN-γ产生和细胞毒性T细胞活性增强。IL-28的抗肿瘤作用部分依赖于IFN-γ，而不依赖于IL-12、IL-17和IL-23。IL-28增加了SCID小鼠脾NK细胞的总数，增强了IL-12诱导的体内IFN-γ产生，并扩增了C57 BL/6小鼠的脾细胞。此外，在IFN-γ存在或不存在的情况下，IL-12增强IL-28介导的抗肿瘤活性。这些发现表明IL-28具有诱导针对肿瘤的先天性和适应性免疫应答的生物活性。
IL-28 is a recently. described antiviral cytokine. In this study, we investigated the biological effects of IL-28 on tumor growth to evaluate its antitumor activity. IL-28 or retroviral transduction of the IL-28 gene into MCA205 cells did not affect in vitro growth, whereas in vivo growth of MCA205IL-28 was markedly suppressed along with survival advantages when compared with that of controls. When the metastatic ability of IL-28-secreting MCA205 cells was compared with that of controls, the expression of IL-28 resulted in a potent inhibition of metastases formation in the lungs. IL-28-mediated suppression of tumor growth was mostly abolished in irradiated mice, indicating that irradiation-sensitive cells, presumably immune cells, are primarily involved in the IL-28-induced suppression of tumor growth. In vivo cell depletion experiments displayed that polymorphonuclear neutrophils, NK cells, and CD8 T cells, but not CD4 T Fells, play an equal role in the IL-28-mediated inhibition of in vivo tumor growth. Consistent with these findings, inoculation of MCA205IL-28 into mice evoked enhanced IFN-gamma production and cytotoxic T cell activity in spleen cells. Antitumor action of IL-28 is partially dependent on IFN-gamma and is independent of IL-12, IL-17, and IL-23. IL-28 increased the total number of splenic NK cells in SCID mice and enhanced IL-12-induced IFN-gamma production in vivo and expanded spleen cells in C57BL/6 mice. Moreover, IL-12 augmented IL-28-mediated antitumor activity in the presence or absence of IFN-gamma. These findings indicate that IL-28 has bioactivities that induce innate and adaptive immune responses against tumors.