Interleukin-7-dependent expansion and persistence of melanoma-specific T cells in lymphodepleted mice lead to tumor regression and editing
Interleukin-7-dependent expansion and persistence of melanoma-specific T cells in lymphodepleted mice lead to tumor regression and editing
复制标题
淋巴清除小鼠中黑色素瘤特异性 T 细胞依赖白介素 7 的扩增和持续存在导致肿瘤消退和编辑
DOI：
10.1158/0008-5472.can-05-2117
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发表时间：
2005-11-15
期刊：
影响因子：
11.2
通讯作者：
Hu, HM
中科院分区：
文献类型：
--
作者：
Wang, LX;Li, R;Hu, HM
用负载有来自黑色素瘤抗原gp 100的肽的树突状细胞的活性特异性免疫疗法未能介导正常小鼠中已建立的B16 F10黑色素瘤的消退。在正常小鼠中，树突状细胞疫苗接种诱导过继转移的幼稚CD 8（+）T细胞受体转基因（pmel-1）T细胞的活化和随后的缺失，所述幼稚CD 8（+）T细胞受体转基因（pmel-1）T细胞对gpl 00具有特异性。在淋巴细胞耗竭的小鼠中，树突状细胞疫苗接种产生了更大的T细胞扩增，记忆T细胞的长期持久性和肿瘤消退。大多数在功能性记忆T细胞存在下持续存在的肿瘤已经失去或表现出MHC I类或gp 100蛋白的表达减少。与其他幼稚T细胞相比，过继转移至淋巴细胞耗竭小鼠的pmel-1 T细胞在暴露于肽脉冲树突状细胞后表现出更快的增殖和更分化的表型。pmel-1 T细胞的增殖和持久性高度依赖于辐射小鼠中的白细胞介素-7（IL-7），以及当IL-7被中和时的IL-15，这两种关键的稳态细胞因子响应于辐射诱导的淋巴细胞耗竭而产生。
Active-specific immunotherapy with dendritic cells loaded with peptide derived from the melanoma antigen, gp100, failed to mediate regression of established B16F10 melanoma in normal mice. Dendritic cell vaccination induced activation and subsequent deletion of adoptively transferred naive CD8(+) T-cell receptor transgenic (pmel-1) T cells specific for gpl00 in normal mice. In lymphodepleted mice, dendritic cell vaccination produced greater T-cell expansion, long-term persistence of memory T cells, and tumor regression. Most tumors that persisted in the presence of functional memory T cells had either lost or exhibited reduced expression of MHC class I or gp100 proteins. In contrast to other naive T cells, pmel-1 T cells adoptively transferred to lymphodepleted mice exhibited faster proliferation and a more differentiated phenotype after exposure to peptide-pulsed dendritic cells. Proliferation and persistence of pmel-1 T cells was highly dependent on interieukin-7 (IL-7) in irradiated mice, and IL-15 when IL-7 was neutralized, two critical homeostatic cytokines produced in response to the irradiation-induced lymphodepletion.