The Immunization Site of Cytokine-Secreting Tumor Cell Vaccines Influences the Trafficking of Tumor-Specific T Lymphocytes and Antitumor Efficacy against Regional Tumors1
The Immunization Site of Cytokine-Secreting Tumor Cell Vaccines Influences the Trafficking of Tumor-Specific T Lymphocytes and Antitumor Efficacy against Regional Tumors1
复制标题
细胞因子分泌型肿瘤细胞疫苗的免疫位点影响肿瘤特异性 T 淋巴细胞的运输和局部肿瘤的抗肿瘤功效1
作者：
Chun;Kuo;S. Roffler;L. Hwang
经过改造以分泌细胞因子的肿瘤细胞（称为肿瘤细胞疫苗）通常可以产生全身抗肿瘤免疫力，并且在许多情况下会导致肿瘤消退。我们比较了s.c.免疫或肝内免疫表达GM-CSF的肿瘤细胞疫苗对s.c.或原位肝肿瘤。化学转化的肝上皮细胞系，GP 7 TB，来自Fischer 344大鼠，用于产生肿瘤模型和肿瘤细胞疫苗。我们的结果表明，两个s.c.注射辐照的肿瘤细胞疫苗显著控制了s.c.肿瘤，但对原位肝肿瘤完全无效。与皮下注射相比，肝肿瘤中的效应细胞浸润显著减少。肿瘤的与s.c.相比，在肝肿瘤中观察到一些效应细胞的凋亡增强。肿瘤的此外，s.c.免疫优先迁移到s.c.肿瘤部位，如过继转移实验所示。相比之下，使用与携带GM-CSF基因的腺病毒混合的亲本肿瘤细胞的肝内免疫，对肝肿瘤产生了比对s.c.肿瘤的连续转移实验进一步证实了肝脏免疫诱导的T细胞优先迁移到肝脏肿瘤部位。我们的研究结果表明，不同的T细胞群诱导不同的免疫途径。因此，T细胞的归巢行为取决于免疫途径，是决定局部肿瘤免疫治疗疗效的重要因素。
Tumor cells engineered to secrete cytokines, referred to as tumor cell vaccines, can often generate systemic antitumor immunity and, in many cases, cause tumor regression. We compared the efficacy of s.c. immunization or intrahepatic immunization of GM-CSF-expressing tumor cell vaccines on the growth of s.c. or orthotopic liver tumors. A chemically transformed hepatic epithelial cell line, GP7TB, derived from Fischer 344 rats, was used to generate tumor models and tumor cell vaccines. Our results demonstrated that two s.c. injections of an irradiated tumor cell vaccine significantly controlled the growth of s.c. tumors, but was completely ineffective against orthotopic liver tumors. Effector cell infiltration in liver tumors was markedly reduced compared with s.c. tumors. Enhanced apoptosis of some effector cells was observed in the liver tumors compared with the s.c. tumors. Furthermore, the T cells induced by s.c. immunization preferentially migrated to s.c. tumor sites, as demonstrated by adoptive transfer experiments. In contrast, intrahepatic immunization, using parental tumor cells admixed with adenoviruses carrying the GM-CSF gene, yielded significantly better therapeutic effects on the liver tumors than on the s.c. tumors. Adoptive transfer experiments further confirmed that the T cells induced by liver immunization preferentially migrated to the liver tumor sites. Our results demonstrate that distinct T cell populations are induced by different immunization routes. Thus, the homing behavior of T cells depends on the route of immunization and is an important factor determining the efficacy of immunotherapy for regional tumors.
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人粘膜地址素细胞粘附分子-1优先在肠道和相关淋巴组织中表达。
DOI：
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发表时间：
1997
期刊：
The American journal of pathology
影响因子：
--
作者：
Briskin,M;Winsor-Hines,D;Shyjan,A;Cochran,N;Bloom,S;Wilson,J;McEvoy,LM;Butcher,EC;Kassam,N;Mackay,CR;Newman,W;Ringler,DJ
通讯作者：
Ringler,DJ
使用细胞因子基因修饰的肿瘤疫苗对膀胱癌进行免疫治疗。
影响因子：
11.2
作者：
Saito,S;Bannerji,R;Gansbacher,B;Rosenthal,FM;Romanenko,P;Heston,WD;Fair,WR;Gilboa,E
通讯作者：
Gilboa,E
影响因子：
11.2
作者：
C. Armstrong;R. Botella;T. H. Galloway;Nancy B. Murray;Jill Kramp;I. S. Song;J. Ansel
通讯作者：
C. Armstrong;R. Botella;T. H. Galloway;Nancy B. Murray;Jill Kramp;I. S. Song;J. Ansel
影响因子：
32.4
作者：
HUANG, L;SOLDEVILA, G;CRISPE, IN
通讯作者：
CRISPE, IN
影响因子：
3.5
作者：
ADRA, CN;BOER, PH;MCBURNEY, MW
通讯作者：
MCBURNEY, MW