Tumor growth enhances cross-presentation leading to limited T cell activation without tolerance
Tumor growth enhances cross-presentation leading to limited T cell activation without tolerance
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DOI：
10.1084/jem.20010032
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发表时间：
2002-02-18
影响因子：
15.3
通讯作者：
Ohashi, PS
中科院分区：
文献类型：
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作者：
Nguyen, LT;Elford, AR;Ohashi, PS
使用表达确定的肿瘤相关抗原的自发产生的胰岛素瘤的肿瘤模型，我们研究了肿瘤生长是否促进肿瘤特异性T细胞的交叉呈递和耐受。我们发现，所有晚期肿瘤负荷增强肿瘤相关抗原向高亲和力肿瘤特异性T细胞的交叉呈递，诱导T细胞增殖和体内有限的效应子功能。然而，与其他模型相反，尽管肿瘤负荷高，但肿瘤特异性T细胞不耐受。事实上，在荷瘤小鼠中，过继转移的肿瘤特异性T细胞的持久性和反应性增强。因此，可以通过静脉内施用肿瘤衍生肽和激动性抗CD40抗体或病毒免疫和再免疫来引发有效的T细胞介导的抗肿瘤应答。因此，在该模型中，肿瘤生长促进高亲和力肿瘤特异性细胞的活化，而不是耐受性。因此，宿主对T细胞免疫疗法保持应答。
Using a tumor model of spontaneously arising insulinomas expressing a defined tumor-associated antigen, we investigated whether tumor growth promotes cross-presentation and tolerance of tumor-specific T cells. We found that all advanced tumor burden enhanced cross-presentation of tumor-associated antigens to high avidity tumor-specific T cells, inducing T cell proliferation and limited effector function in vivo. However, contrary to other models, tumor-specific T cells were not tolerized despite a high tumor burden. In fact, in tumor-bearing mice, persistence and responsiveness of adoptively transferred tumor-specific T cells were enhanced. Accordingly, a potent T cell-mediated antitumor response could be elicited by intravenous administration of tumor-derived peptide and agonistic anti-CD40 antibody or viral immunization and reimmunization. Thus, in this model, tumor growth promotes activation of high avidity tumor-specific cells instead of tolerance. Therefore, the host remains responsive to T cell immunotherapy.