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对接受HER2/neu肽(E75)和GM-CSF疫苗的乳腺癌患者中初始和记忆性CD4和CD8 T细胞群体的分析。

Analysis of naïve and memory CD4 and CD8 T cell populations in breast cancer patients receiving a HER2/neu peptide (E75) and GM-CSF vaccine.

作者信息

Hueman Matthew T, Stojadinovic Alexander, Storrer Catherine E, Dehqanzada Zia A, Gurney Jennifer M, Shriver Craig D, Ponniah Sathibalan, Peoples George E

机构信息

Clinical Breast Care Project, Department of Surgery, Walter Reed Army Medical Center, Washington, DC 20307, USA.

出版信息

Cancer Immunol Immunother. 2007 Feb;56(2):135-46. doi: 10.1007/s00262-006-0188-9. Epub 2006 Jun 17.

Abstract

We are conducting clinical trials of the E75 peptide as a vaccine in breast cancer (BrCa) patients. We assessed T cell subpopulations in BrCa patients before and after E75 vaccination and compared them to healthy controls. We obtained 17 samples of blood from ten healthy individuals and samples from 22 BrCa patients prior to vaccination. We also obtained pre- and post-vaccination samples of blood from seven BrCa patients who received the E75/GM-CSF vaccine. CD4, CD8, CD45RA, CD45RO, and CCR7 antibodies were used to analyze the CD4+ and CD8+ T cells by four-color flow cytometry. Compared to healthy individuals, BrCa patients have significantly more memory and less naïve T cells and more effector-memory CD8+ and less effector CD4+ T cells. Phenotypic differences in defined circulating CD4+ and CD8+ T cell subpopulations suggest remnants of an active immune response to tumor distinguished by a predominant memory T cell response and by untapped recruitment of naïve helper and cytotoxic T cells. E75 vaccination induced recruitment of both CD4+ and CD8+ naïve T cells while memory response remained stable. Additionally, vaccination induced global activation of all T cells, with specific enhancement of effector CD4+ T cells. E75 vaccination causes activation of both memory and naïve CD4+ and CD8+ T cells, while recruiting additional naïve CD4+ and CD8+ T cells to the overall immune response.

摘要

我们正在进行E75肽作为乳腺癌(BrCa)患者疫苗的临床试验。我们评估了E75疫苗接种前后BrCa患者的T细胞亚群,并将其与健康对照进行比较。我们从10名健康个体中获取了17份血液样本,以及22名BrCa患者在接种疫苗前的样本。我们还从7名接受E75/GM-CSF疫苗的BrCa患者中获取了接种疫苗前后的血液样本。使用CD4、CD8、CD45RA、CD45RO和CCR7抗体通过四色流式细胞术分析CD4+和CD8+T细胞。与健康个体相比,BrCa患者具有显著更多的记忆性T细胞和更少的初始T细胞,以及更多的效应记忆性CD8+T细胞和更少的效应性CD4+T细胞。特定循环CD4+和CD8+T细胞亚群的表型差异表明,对肿瘤的活跃免疫反应的残余特征是主要的记忆性T细胞反应以及未被利用的初始辅助性和细胞毒性T细胞的募集。E75疫苗接种诱导了CD4+和CD8+初始T细胞的募集,而记忆反应保持稳定。此外,疫苗接种诱导了所有T细胞的整体激活,特别是效应性CD4+T细胞的增强。E75疫苗接种导致记忆性和初始CD4+和CD8+T细胞的激活,同时在整体免疫反应中募集额外的初始CD4+和CD8+T细胞。

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