Marked differences in human melanoma antigen-specific T cell responsiveness after vaccination using a functional microarray.
Marked differences in human melanoma antigen-specific T cell responsiveness after vaccination using a functional microarray.
复制标题
使用功能性微阵列接种后，人类黑色素瘤特异性T细胞反应性的明显差异。
DOI：
10.1371/journal.pmed.0020265
复制
发表时间：
2005-10
期刊：
影响因子：
15.8
通讯作者：
Davis, MM
中科院分区：
文献类型：
--
作者：
Chen, DS;Soen, Y;Stuge, TB;Lee, PP;Weber, JS;Brown, PO;Davis, MM
与许多动物模型研究相反，对患有癌症的人类进行的免疫治疗试验总是会产生广泛的结果，从长期缓解到没有明显效果。为了研究接受黑色素瘤相关肽疫苗试验的患者的 T 细胞反应，我们开发了一种高通量方法，使用肽主要组织相容性复合物 (pMHC) 阵列以及针对分泌因子的抗体。 T 细胞通过与特定的 pMHC 结合而被特异性固定和激活。这些抗体与 pMHC 一起发现，特异性捕获 T 细胞分泌的细胞因子。该技术可以对临床样本中存在的抗原特异性 T 细胞进行快速、同步分离和多参数功能表征。对肽疫苗接种后 10 名黑色素瘤患者的 CD8+ 淋巴细胞进行的分析揭示了细胞因子分泌的多种患者和抗原特异性谱，表明它们的反应性存在惊人的差异。响应 gp100 抗原而表现出中度或大量分泌干扰素-γ (IFNγ) 和肿瘤坏死因子-α (TNFα) 的患者中，四分之四的患者没有出现黑色素瘤复发，而表现出 IFNγ 和 TNFα 分泌不一致的六名患者中只有两名出现这种情况。这种对 T 细胞抗原特异性和功能的多参数分析提供了一个有价值的工具，可以用来剖析免疫反应的分子基础以及这些信息如何与临床结果相关。接种黑色素瘤相关肽疫苗的患者表现出多种多样的反应，对其进行分析可能有助于我们了解对此类疫苗的不同临床反应。
In contrast to many animal model studies, immunotherapeutic trials in humans suffering from cancer invariably result in a broad range of outcomes, from long-lasting remissions to no discernable effect. In order to study the T cell responses in patients undergoing a melanoma-associated peptide vaccine trial, we have developed a high-throughput method using arrays of peptide-major histocompatibility complexes (pMHC) together with antibodies against secreted factors. T cells were specifically immobilized and activated by binding to particular pMHCs. The antibodies, spotted together with the pMHC, specifically capture cytokines secreted by the T cells. This technique allows rapid, simultaneous isolation and multiparametric functional characterization of antigen-specific T cells present in clinical samples. Analysis of CD8+ lymphocytes from ten melanoma patients after peptide vaccination revealed a diverse set of patient- and antigen-specific profiles of cytokine secretion, indicating surprising differences in their responsiveness. Four out of four patients who showed moderate or greater secretion of both interferon-γ (IFNγ) and tumor necrosis factor-α (TNFα) in response to a gp100 antigen remained free of melanoma recurrence, whereas only two of six patients who showed discordant secretion of IFNγ and TNFα did so. Such multiparametric analysis of T cell antigen specificity and function provides a valuable tool with which to dissect the molecular underpinnings of immune responsiveness and how this information correlates with clinical outcome. Patients vaccinated with melanoma-associated peptides show a wide diversity of responses, analysis of which may help us understand the differing clinical responses to such vaccines.
登录
查看更多内容
影响因子：
14.5
作者：
Andersen, MH;Gehl, J;Straten, PT
通讯作者：
Straten, PT
影响因子：
8.7
作者：
GRONVIK, KO;ANDERSSON, J
通讯作者：
ANDERSSON, J
影响因子：
56.9
作者：
Altman, JD;Moss, PAH;Davis, MM
通讯作者：
Davis, MM
DOI：
10.1073/pnas.90.14.6671
发表时间：
1993-07-15
影响因子：
11.1
作者：
DALPORTO, J;JOHANSEN, TE;SCHNECK, JP
通讯作者：
SCHNECK, JP
DOI：
10.3109/08820137209022939
发表时间：
1972-01-01
期刊：
IMMUNOLOGICAL COMMUNICATIONS
影响因子：
--
作者：
JOHNSON, TR;DEINHARDT, F;MASSEY, RJ
通讯作者：
MASSEY, RJ