Mesothelin-specific CD8(+) T cell responses provide evidence of in vivo cross-priming by antigen-presenting cells in vaccinated pancreatic cancer patients.
Mesothelin-specific CD8(+) T cell responses provide evidence of in vivo cross-priming by antigen-presenting cells in vaccinated pancreatic cancer patients.
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DOI：
10.1084/jem.20031435
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发表时间：
2004-08-02
期刊：
影响因子：
--
通讯作者：
Jaffee EM
中科院分区：
文献类型：
--
作者：
Thomas AM;Santarsiero LM;Lutz ER;Armstrong TD;Chen YC;Huang LQ;Laheru DA;Goggins M;Hruban RH;Jaffee EM
肿瘤特异性CD8+T细胞可能被主要组织相容性复合体I类限制性抗原提呈的两种不同机制激活：由肿瘤细胞自身直接提呈或由专业抗原提呈细胞(APC)间接提呈。然而，对于间接呈现(交叉启动机制)是否有助于在体内有效地激活能够根除患者癌症的肿瘤特异性CD8+T细胞，仍然存在争议。设计了一项用粒细胞巨噬细胞集落刺激因子转导的胰腺癌细胞系接种的临床试验，以测试局部招募的APC交叉呈现是否能激活胰腺肿瘤特异性CD8+T细胞。在此之前，我们报告了14例接受治疗的患者中有3例出现了疫苗接种后对自体肿瘤的迟发性超敏反应。间皮蛋白是一种抗原，以前通过基因表达谱证明在大多数胰腺癌中上调。我们在此报道，在疫苗诱导的DTH反应的三名患者中，CD8+T细胞对多种限制的HLA-A2、A3和A24限制的间皮蛋白表位的反应是一致的。重要的是，接种的两个胰腺癌细胞株都没有表达HLA-A2、A3或A24。这些结果提供了第一个直接证据，表明CD8 T细胞反应可以通过免疫治疗方法通过交叉呈现产生，该方法旨在将APC招募到疫苗接种地点。
Tumor-specific CD8+ T cells can potentially be activated by two distinct mechanisms of major histocompatibility complex class I–restricted antigen presentation as follows: direct presentation by tumor cells themselves or indirect presentation by professional antigen-presenting cells (APCs). However, controversy still exists as to whether indirect presentation (the cross-priming mechanism) can contribute to effective in vivo priming of tumor-specific CD8+ T cells that are capable of eradicating cancer in patients. A clinical trial of vaccination with granulocyte macrophage–colony stimulating factor–transduced pancreatic cancer lines was designed to test whether cross-presentation by locally recruited APCs can activate pancreatic tumor-specific CD8+ T cells. Previously, we reported postvaccination delayed-type hypersensitivity (DTH) responses to autologous tumor in 3 out of 14 treated patients. Mesothelin is an antigen demonstrated previously by gene expression profiling to be up-regulated in most pancreatic cancers. We report here the consistent induction of CD8+ T cell responses to multiple HLA-A2, A3, and A24-restricted mesothelin epitopes exclusively in the three patients with vaccine-induced DTH responses. Importantly, neither of the vaccinating pancreatic cancer cell lines expressed HLA-A2, A3, or A24. These results provide the first direct evidence that CD8 T cell responses can be generated via cross-presentation by an immunotherapy approach designed to recruit APCs to the vaccination site.
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影响因子：
32.4
作者：
Jung, S;Unutmaz, D;Lang, RA
通讯作者：
Lang, RA
DOI：
10.1084/jem.192.12.1685
发表时间：
2000-12-18
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
den Haan JM;Lehar SM;Bevan MJ
通讯作者：
Bevan MJ
影响因子：
56.9
作者：
KOVACSOVICSBANKOWSKI, M;ROCK, KL
通讯作者：
ROCK, KL
影响因子：
56.9
作者：
Altman, JD;Moss, PAH;Davis, MM
通讯作者：
Davis, MM
DOI：
10.1073/pnas.202491499
发表时间：
2002-10-01
影响因子：
11.1
作者：
Dhodapkar, MV;Krasovsky, J;Olson, K
通讯作者：
Olson, K