Recruitment of latent pools of high-avidity CD8(+) T cells to the antitumor immune response.
Recruitment of latent pools of high-avidity CD8(+) T cells to the antitumor immune response.
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募集高危险性CD8（+）T细胞的潜在池募集到抗肿瘤免疫反应中。
DOI：
10.1084/jem.20042167
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发表时间：
2005-05-16
期刊：
影响因子：
--
通讯作者：
Jaffee EM
中科院分区：
文献类型：
--
作者：
Ercolini AM;Ladle BH;Manning EA;Pfannenstiel LW;Armstrong TD;Machiels JP;Bieler JG;Emens LA;Reilly RT;Jaffee EM
成功的抗肿瘤疫苗接种的主要障碍是对肿瘤抗原特异性的高亲和力T细胞的耐受性。与此观点一致，HER-2/neu（neu）靶向疫苗在WT FVB/N小鼠中对显性肽（RNEU 420 -429）产生强烈的CD 8 + T细胞应答，并保护它们免受表达neu的肿瘤攻击，但在MMTV-neu（neu-N）转基因小鼠中未能做到这一点。然而，用疫苗和含环磷酰胺的化疗治疗neu-N小鼠导致一定比例的小鼠的肿瘤保护。这种作用通过neu-N-衍生的CD 4 + CD 25 + T细胞的转移而特异性地消除。RNEU 420 -429特异性CD 8 + T细胞仅在接受疫苗和环磷酰胺化疗的neu-N小鼠中鉴定，这些小鼠拒绝肿瘤攻击。四聚体结合研究表明，环磷酰胺预处理允许高亲合力RNEU 420 -429特异性CD 8 + T细胞的活化，与接种FVB/N小鼠产生的T细胞相当。环磷酰胺似乎通过选择性地消耗neu-N小鼠中的CD 4 + CD 25 + T细胞的循环群体来抑制调节性T（T reg）细胞。这些发现表明，neu-N小鼠具有高亲合力neu特异性CD 8 + T细胞的潜伏池，如果在接种前使用环磷酰胺等方法阻断或去除T reg细胞，则可以招募这些细胞以产生有效的抗肿瘤应答。
A major barrier to successful antitumor vaccination is tolerance of high-avidity T cells specific to tumor antigens. In keeping with this notion, HER-2/neu (neu)-targeted vaccines, which raise strong CD8+ T cell responses to a dominant peptide (RNEU420-429) in WT FVB/N mice and protect them from a neu-expressing tumor challenge, fail to do so in MMTV-neu (neu-N) transgenic mice. However, treatment of neu-N mice with vaccine and cyclophosphamide-containing chemotherapy resulted in tumor protection in a proportion of mice. This effect was specifically abrogated by the transfer of neu-N–derived CD4+CD25+ T cells. RNEU420-429-specific CD8+ T cells were identified only in neu-N mice given vaccine and cyclophosphamide chemotherapy which rejected tumor challenge. Tetramer-binding studies demonstrated that cyclophosphamide pretreatment allowed the activation of high-avidity RNEU420-429-specific CD8+ T cells comparable to those generated from vaccinated FVB/N mice. Cyclophosphamide seemed to inhibit regulatory T (T reg) cells by selectively depleting the cycling population of CD4+CD25+ T cells in neu-N mice. These findings demonstrate that neu-N mice possess latent pools of high-avidity neu-specific CD8+ T cells that can be recruited to produce an effective antitumor response if T reg cells are blocked or removed by using approaches such as administration of cyclophosphamide before vaccination.
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DOI：
10.1084/jem.187.10.1555
发表时间：
1998-05-18
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Adler AJ;Marsh DW;Yochum GS;Guzzo JL;Nigam A;Nelson WG;Pardoll DM
通讯作者：
Pardoll DM
影响因子：
4.4
作者：
Hernández, J;Ko, A;Sherman, LA
通讯作者：
Sherman, LA
影响因子：
56.9
作者：
Altman, JD;Moss, PAH;Davis, MM
通讯作者：
Davis, MM
影响因子：
15.3
作者：
Heath, W R;Kurts, C;Miller, J F;Carbone, F R
通讯作者：
Carbone, F R
影响因子：
5.4
作者：
Ghiringhelli, F;Larmonier, N;Martin, F
通讯作者：
Martin, F