Secretion of stress protein grp170 promotes immune-mediated inhibition of murine prostate tumor.
Secretion of stress protein grp170 promotes immune-mediated inhibition of murine prostate tumor.
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DOI：
10.1007/s00262-008-0647-6
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发表时间：
2009-08
期刊：
影响因子：
--
通讯作者：
Wang XY
中科院分区：
文献类型：
--
作者：
Gao P;Sun X;Chen X;Subjeck J;Wang XY
众所周知，某些应激蛋白或分子伴侣在交叉呈递肿瘤衍生抗原方面非常有效，从而产生有效的抗肿瘤免疫反应。在这项研究中，我们证明，通过用可分泌形式的内质网驻留分子伴侣 grp170 稳定转染，对弱免疫原性小鼠前列腺肿瘤细胞 (TRAMP-C2) 进行遗传修饰，可显着增强其体内免疫原性。远处亲本肿瘤的生长抑制表明产生了全身抗肿瘤免疫，这与肿瘤浸润增加、CD8+ T 细胞效应功能增强有关。使用灭活的 grp170 分泌 C2 细胞进行免疫增强了 CD8+ T 细胞依赖性肿瘤保护作用。此外，用编码可分泌型 grp170 的非复制腺病毒载体感染 C2 肿瘤细胞比质粒转导更有效地促进肿瘤免疫原性，树突细胞促炎细胞因子 TNF-α 的产生增加，并增强治疗预先形成的肿瘤的疗效。鉴于前列腺肿瘤中存在未定义的抗原，当与其他治疗方式相结合时，操纵免疫刺激伴侣 grp170 的细胞区室化以引发全身肿瘤免疫可用于改善前列腺癌的治疗结果。
It is well established that certain stress proteins or molecular chaperones are highly efficient in cross-presenting tumor-derived antigens, resulting in a potent antitumor immune response. In this study we demonstrate that genetic modification of weakly immunogenic murine prostate tumor cells (TRAMP-C2) by stable transfection with a secretable form of endoplasmic reticulum resident chaperone grp170 significantly enhances its immunogenicity in vivo. Generation of systemic antitumor immunity is indicated by the growth suppression of distant parental tumors, which is associated with increased tumor infiltration, elevated effector functions of CD8+ T-cells. Immunization with inactivated grp170-secreting C2 cells augments a CD8+ T-cell dependent, tumor-protective effect. Furthermore, infection of C2 tumor cells with a nonreplicating adenoviral vectors encoding secretable grp170 promotes tumor immunogenicity more effectively than plasmid transduction, as shown by the increased production of pro-inflammatory cytokine TNF-α by dendritice cells and enhanced therapeutic efficacy in treating pre-established tumors. Given a repertoire of undefined antigens in prostate tumor, manipulation of cellular compartmentalization of immuno-stimulatory chaperone grp170 to elicit systemic tumor immunity may be used to improve treatment outcomes for prostate cancer when combined with other treatment modalities.
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DOI：
10.1093/jnci/87.4.280
发表时间：
1995-02-15
期刊：
JOURNAL OF THE NATIONAL CANCER INSTITUTE
影响因子：
--
作者：
SANDA, MG;RESTIFO, NP;SIMONS, JW
通讯作者：
SIMONS, JW
影响因子：
11.2
作者：
Massa, C;Guiducci, C;Melani, C
通讯作者：
Melani, C
影响因子：
32.4
作者：
MacAry, PA;Javid, B;Lehner, PJ
通讯作者：
Lehner, PJ
影响因子：
4
作者：
Manjili, MH;Park, JE;Subjeck, JR
通讯作者：
Subjeck, JR
影响因子：
82.9
作者：
Melcher, A;Todryk, S;Vile, RG
通讯作者：
Vile, RG