Expression of IL-27 in murine carcinoma cells produces antitumor effects and induces protective immunity in inoculated host animals
Expression of IL-27 in murine carcinoma cells produces antitumor effects and induces protective immunity in inoculated host animals
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DOI：
10.1002/ijc.20848
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发表时间：
2005-06-20
影响因子：
6.4
通讯作者：
Tagawa, M
中科院分区：
文献类型：
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作者：
Chiyo, M;Shimozato, O;Tagawa, M
一种新的细胞因子白细胞介素-27（IL-27）由p28和EB病毒诱导基因3（EBI 3）组成，由活化的树突状细胞产生，并参与T辅助细胞I型分化的早期阶段。我们研究了逆转录病毒转导p28连接的EBI 3基因（Colon 26/IL-27）的Colon 26小鼠结肠癌细胞是否能在接种小鼠中产生抗肿瘤作用。虽然Colon 26/IL-27细胞的体外增殖与亲本细胞没有差异，但同基因BALB/c小鼠排斥接种的Colon 26/IL-27肿瘤，随后获得肿瘤特异性保护性免疫。相反，用p28或EBI 3基因转导的Colon 26细胞接种的小鼠发生肿瘤，小鼠的存活率与接种亲本细胞的小鼠相同。同系裸鼠发生结肠26/IL-27肿瘤，但与亲代肿瘤相比生长迟缓。用抗去唾液酸GM抗体耗尽来自裸鼠的自然杀伤细胞减少了结肠26/IL-27肿瘤的生长迟缓。皮下接种Colon 26/IL-27细胞的严重联合免疫缺陷小鼠的存活率与接种亲本细胞的免疫缺陷小鼠的存活率没有差异。从CD 4（+）和CD 8（+）T产生干扰素-γ，并且还从小鼠中检测到排斥Colon 26/IL-27肿瘤的小鼠的自然杀伤细胞和针对Colon 26细胞的细胞毒活性。这些数据共同表明，在肿瘤中表达的IL-27产生T细胞依赖性和非依赖性抗肿瘤作用，并且是癌症的可能治疗策略。(c)2005 Wiley-Liss，Inc.
A novel cytokine interieukin-27 (IL-27), composed of p28 and Epstein-Barr virus-induced gene 3 (EBI3), is produced from activated dendritic cells and is involved in an early phase of T-helper type I differentiation. We examined whether Colon 26 murine colon carcinoma cells that were retrovirally transduced with the p28-linked EBI3 gene (Colon 26/IL-27) could produce antitumor effects in inoculated mice. Although proliferation in vitro of Colon 26/IL-27 cells was not different from that of parent cells, syngeneic BALB/c mice rejected Colon 26/IL-27 tumors inoculated and subsequently acquired tumor-specific protective immunity. In contrast, mice inoculated with Colon 26 cells transduced with either the p28 or EBI3 gene developed tumors and survival of the mice remained the same as that of the mice inoculated with parent cells. Syngeneic nude mice developed Colon 26/IL-27 tumors, but the growth was retarded compared to that of parent tumors. Depletion of natural killer cells from nude mice with anti-asialo GM, antibody diminished the growth retardation of Colon 26/IL-27 tumors. Survival of severe combined immunodeficient mice that received subcutaneous inoculation of Colon 26/IL-27 cells was not different from that of the immunodeficient mice inoculated with parent cells. Interferon-gamma was produced from CD4(+) and CD8(+) T, and natural killer cells of the mice that rejected Colon 26/IL-27 tumors and cytotoxic activity against Colon 26 cells were also detected from the mice. These data collectively suggest that expressed IL-27 in tumors produces T cell-dependent and-independent antitumor effects and is a possible therapeutic strategy for cancer. (c) 2005 Wiley-Liss, Inc.