Antitumor Effects on Mouse Melanoma Elicited by Local Secretion of Interleukin-12 and Their Enhancement by Treatment with Interleukin-18
Antitumor Effects on Mouse Melanoma Elicited by Local Secretion of Interleukin-12 and Their Enhancement by Treatment with Interleukin-18
复制标题
局部分泌白细胞介素 12 引起的小鼠黑色素瘤的抗肿瘤作用及其通过白细胞介素 18 治疗的增强
作者：
H. Nagai;I. Hara;T. Horikawa;M. Fujii;M. Kurimoto;S. Kamidono;M. Ichihashi
为探讨局部分泌白细胞介素12（IL-12）抗肿瘤作用的机制，我们将IL-12 p35和p40 cDNA导入小鼠B16黑色素瘤细胞。IL-12基因转染的B16黑色素瘤（B16/IL-12）皮下植入同系小鼠后，肿瘤生长明显迟缓。在这些小鼠中，不仅自然杀伤（NK）细胞，而且CD 8 + T细胞的耗竭减少了局部分泌的IL-12的抗肿瘤作用。免疫组化分析显示，NK细胞和巨噬细胞聚集在B16/IL 12肿瘤的中心和周边比亲本B16肿瘤，而CD 4 + T细胞和CD 8 + T细胞聚集稀疏，仅在周围的转染和未转染的肿瘤。全身用白细胞介素-18（IL-18）治疗可显著抑制B16/IL-12的生长，但不影响亲本B16细胞的体内肿瘤生长。这些结果表明，局部IL-12分泌可以延缓主要由NK细胞介导和间接由CD 8 + T细胞介导的B16黑色素瘤的生长，并且其抗肿瘤作用通过用新型细胞因子IL-18进行全身治疗而增强。
Abstract To investigate the mechanism of the antitumor effect of locally secreted interleukin-12 (IL-12), we introduced the IL-12 p35 and p40 cDNAs into mouse B16 melanoma cells. IL-12 gene-transfected B16 melanoma (B16/IL12) showed marked retardation of tumor growth when implanted subcutaneously into syngeneic mice. In these mice, depletion of not only Natural Killer (NK) cells but also CD8+ T cells diminished the antitumor effect of locally secreted IL-12. Immunohistochemical analysis showed that NK cells and macrophages accumulated more densely at the center and periphery of B16/IL12 tumors than that of parental B16 tumors, whereas CD4+ T cells and CD8+ T cells accumulated sparsely only at the periphery of both transfected and untransfected tumors. Systemic treatment with interleukin-18 (IL-18) markedly inhibited the growth of B16/IL12 but did not influence the tumor growth of parental B16 cells in vivo. These results suggest that local IL-12 secretion can retard the growth of B16 melanoma mediated primarily by NK cells and indirectly by CD8+ T cells and that its antitumor effect is augmented by systemic treatment with the novel cytokine IL-18.
一种 cDNA 克隆载体，允许在哺乳动物细胞中表达 cDNA 插入片段。
影响因子：
5.3
作者：
Okayama,H;Berg,P
通讯作者：
Berg,P
经过基因工程改造后分泌白细胞介素 12 的成纤维细胞可以抑制肿瘤生长，并在体内诱导针对小鼠黑色素瘤的抗肿瘤免疫。
影响因子：
11.2
作者：
Tahara,H;Zeh3rd,HJ;Storkus,WJ;Pappo,I;Watkins,SC;Gubler,U;Wolf,SF;Robbins,PD;Lotze,MT
通讯作者：
Lotze,MT