Transduction of the IL-21 and IL-23 genes in human pancreatic carcinoma cells produces natural killer cell-dependent and -independent antitumor effects
Transduction of the IL-21 and IL-23 genes in human pancreatic carcinoma cells produces natural killer cell-dependent and -independent antitumor effects
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DOI：
10.1038/sj.cgt.7700630
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发表时间：
2003-10-01
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：
Ugai, S;Shimozato, O;Tagawa, M
我们检测了在肿瘤中表达的新的细胞因子IL-21和IL-23是否能在接种的小鼠中产生抗肿瘤作用。将小鼠IL-21或IL-23(p19连接的p40)基因(ASPC-1/IL-21，ASPC-1/IL-23)逆转录导入人胰腺癌ASPC-1细胞，分别接种于裸鼠和重症联合免疫缺陷(SCID)小鼠体内。尽管转导细胞的体外增殖能力与亲本细胞相同，但裸鼠体内的ASPC-1/IL-21和ASPC-1/IL-23肿瘤生长较亲本肿瘤明显减慢。用抗asialo GM(1)抗体处理裸鼠，可暂时消除ASPC-1/IL-21肿瘤的生长抑制，但不能抑制ASPC-1/IL-23肿瘤的生长；然而，随着自然杀伤(NK)细胞的再生，ASPC-1/IL-21肿瘤的生长受到抑制。SCID小鼠体内的ASPC-1/IL-21肿瘤的生长与亲本肿瘤相比也受到抑制，这种生长抑制作用可被抗asialo GM(1)抗体所消除。ASPC-1/IL-23肿瘤在SCID小鼠体内的生长与亲本肿瘤无明显差异。ASPC-1/IL-21或ASPC-1/IL-23荷瘤小鼠的脾细胞对ASPC-1细胞的杀伤活性和干扰素-γ的分泌均有诱导作用。将ASPC-1/IL-21和ASPC-1/IL-23细胞混合接种裸鼠，未观察到协同作用。这些数据共同表明，在Alphabeta T细胞缺陷状态下，IL-21和IL-23在肿瘤中的表达可以分别产生依赖于NK细胞的和非依赖的抗肿瘤效应。
We examined whether novel cytokines, interleukin (IL)-21 and IL-23, that were expressed in tumors could produce antitumor effects in the inoculated mice. Human pancreatic cancer AsPC-1 cells were retrovirally transduced with murine IL-21 or IL-23 (p19-linked p40) gene (AsPC-1/IL-21, AsPC-1/IL-23) and were injected into nude or severe combined immunodeficiency ( SCID) mice. Although the proliferation in vitro of the transduced cells remained the same as that of parent cells, growth of AsPC-1/IL-21 and AsPC-1/IL-23 tumors developed in nude mice was retarded compared with that of parent tumors. Treatment of nude mice with anti-asialo GM(1) antibody temporally abrogated the growth retardation of AsPC-1/IL-21, but not AsPC-1/IL-23 tumors; however, the growth of AsPC-1/IL-21 tumors came to be retarded thereafter with the regeneration of natural killer (NK) cells. The growth of AsPC-1/IL-21 tumors developed in SCID mice was also retarded compared with parent tumors and the growth retardation was abrogated by treatment with anti-asialo GM(1) antibody. The growth of AsPC-1/IL-23 tumors in SCID mice was not different from that of parent tumors. Cytotoxic activity and secretion of interferon-gamma in response to AsPC-1 cells were induced in spleen cells of the mice bearing AsPC-1/IL-21 or AsPC-1/IL-23 tumors. When nude mice were injected with a mixed population of AsPC-1/IL-21 and AsPC-1/IL-23 cells, no synergistic effects were observed. These data collectively suggest that expression of IL-21 and IL-23 in tumors can produce NK cell-dependent and -independent antitumor effects in an alphabeta T cell-defective condition, respectively.