Interleukin-10 inhibits tumor metastasis, downregulates MHC class I, and enhances NK lysis
Interleukin-10 inhibits tumor metastasis, downregulates MHC class I, and enhances NK lysis
复制标题
DOI：
10.1006/cimm.1997.1176
复制
发表时间：
1997-08-25
影响因子：
4.3
通讯作者：
Fulton, AM
中科院分区：
文献类型：
--
作者：
Kundu, N;Fulton, AM
我们设计了高侵袭性小鼠乳腺肿瘤细胞系410.4，使其表达白细胞介素-10（IL-10），并将这些细胞的体内行为与对照质粒（410.4-neo）转染的亲本410.4和410.4进行了比较。将亲代410.4和410.4-neo肿瘤细胞移植到同基因小鼠导致进行性生长和肺转移死亡。相比之下，皮下生长和转移性疾病都被IL-10表达完全抑制。我们先前已经表明，IL-10的抗转移活性在T细胞缺陷小鼠中表达，但当NK活性受到抑制时，IL-10的抗转移活性丧失。该研究证实IL-10依赖于NK活性，因为在缺乏T、B和NK细胞功能的C.B-17/lcrCrl-SCID/Beige小鼠中没有观察到治疗效果。我们比较了4个IL-10表达克隆与410.4和410.4-neo对NK裂解的敏感性，发现IL-10表达导致所有4个克隆的NR裂解增强。此外，IL-10表达与MHC I类K-d、L-d和D-d表面表达的减少相关。用IFN-γ预处理表达IL-10的细胞系逆转了I类下调，并降低了这些细胞对NK细胞溶解的敏感性。总之，这些体外和体内研究与IL-10表达下调I类表达的机制一致，导致肿瘤细胞的NK溶解增强，从而控制转移性疾病。(C)北京：科学出版社.
We have engineered highly aggressive murine mammary tumor cell line 410.4 to express interleukin-10 (IL-10) and compared the behavior in vivo of these cells to parental 410.4 and 410.4 transfected with the control plasmid (410.4-neo). Transplantation of parental 410.4 and 410.4-neo tumor cells to syngeneic mice resulted in progressive growth and death from pulmonary metastases. In contrast, both subcutaneous growth and metastatic disease were completely inhibited by IL-10 expression. We had shown previously that the antimetastatic activity of IL-10 is expressed in T-cell-deficient mice but is lost when NK activity is suppressed. This study confirms that IL-10 is dependent on NK activity, since no therapeutic effect is seen in C.B-17/lcrCrl-SCID/Beige mice which lack T, B, and NK cell function. We compared the sensitivity to NK lysis of four IL-10-expressing clones with 410.4 and 410.4-neo and found that IL-10 expression resulted in enhanced NR lysis of all four clones. Furthermore, IL-10 expression was correlated with decreased surface expression of MHC class I K-d, L-d, and D-d. Pretreatment of IL-10-expressing cell lines with IFN-gamma reversed the class I downregulation and reduced the sensitivity of these cells to NK lysis. Taken together, these studies in vitro and in vivo are consistent with a mechanism by which IL-10 expression downregulates class I expression, leading to enhanced NK lysis of tumor cells, resulting in control of metastatic disease. (C) 1997 Academic Press.