Tumor progression despite efficient tumor antigen cross-presentation and effective "arming" of tumor antigen-specific CTL
Tumor progression despite efficient tumor antigen cross-presentation and effective "arming" of tumor antigen-specific CTL
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DOI：
10.4049/jimmunol.166.9.5557
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发表时间：
2001-05-01
影响因子：
4.4
通讯作者：
Robinson, B
中科院分区：
文献类型：
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作者：
Nelson, DJ;Mukherjee, S;Robinson, B
为了确定APC功能或CTL的裂解功能是否是来自非免疫原性肿瘤的Ag不能诱导有效免疫应答的点，我们建立了表达细胞内OVA的小鼠肿瘤模型，并选择了在肿瘤生长过程中对特异性CD 8（+）T细胞裂解敏感的克隆（cOVA-9）。存活的cOVA-9肿瘤细胞在正常小鼠中以与亲本肿瘤相似的速率生长，并且用辐照过的cOVA-9细胞接种疫苗不会诱导针对其自身或亲本系的保护，证实了其非免疫原性状态。在肿瘤生长过程中的体内评价表明，持续的肿瘤Ag交叉呈递伴随着产生强效的特异性CTL，当肿瘤几乎不可触及时可检测到CTL。尽管在肿瘤引流淋巴结中存在高活性的CTL，但没有明显的肿瘤相关APC溶解。这些数据表明，肿瘤引流APC在两个关键过程（体内肿瘤Ag交叉呈递和特异性CTL武装）方面没有功能障碍，并且未能阻止肿瘤生长不是在诱导阶段，而是在效应阶段，并且在肿瘤基质建立之前发生在肿瘤本身内。
To determine whether APC function or "arming" of CTL for lytic function are the points at which Ags from a nonimmunogenic tumor fail to induce an effective immune response, we established a murine tumor model that expressed intracellular OVA and selected a clone (cOVA-9) that remained susceptible to lysis by specific CD8(+) T cells throughout tumor growth. Viable cOVA-9 tumor cells grew in normal mice at a rate similar to the parental tumor, and vaccination with irradiated cOVA-9 cells did not induce protection against itself or the parental line, confirming its nonimmunogenic status. In vivo evaluation during tumor growth demonstrated persisting tumor Ag cross-presentation accompanied by the generation of potent, specific CTL which were detectable when tumors were barely palpable. Despite the presence of highly active CTL in the tumor-draining lymph nodes, there was no apparent lysis of tumor-associated APC. These data show that tumor-draining APC are not dysfunctional with regard to two crucial processes, in vivo tumor Ag cross-presentation and specific CTL arming, and that failure to prevent tumor growth is not in the induction phase, but in the effector phase and occurs within the tumor itself before the tumor matrix is established.