Cancer Vaccine Enhanced, Non-Tumor-Reactive CD8+ T Cells Exhibit a Distinct Molecular Program Associated with "Division Arrest Anergy"

被引：12

作者：

Beyer, Marc ^{[1
,3
]}

Karbach, Julia ^{[4
]}

Mallmann, Michael R. ^{[1
,3
]}

Zander, Thomas ^{[3
]}

Eggle, Daniela ^{[3
]}

Classen, Sabine ^{[1
,3
]}

Debey-Pascher, Svenja ^{[1
,3
]}

Famulok, Michael ^{[2
]}

Jaeger, Elke ^{[4
]}

Schultze, Joachim L. ^{[1
,3
]}

机构：

[1] Univ Bonn, Lab Genom & Immunoregulat, D-53115 Bonn, Germany

[2] Univ Bonn, Biol Chem Lab, D-53115 Bonn, Germany

[3] Univ Cologne, Cologne, Germany

[4] Krankenhaus NW Frankfurt, Med Klin 2, Frankfurt, Germany

来源：

CANCER RESEARCH | 2009年 / 69卷 / 10期

关键词：

PEPTIDE EPITOPES; IMMUNE-RESPONSE; TGF-BETA; TOLERANCE; RECOGNITION; ACTIVATION; P27(KIP1); ANTIGEN; LYMPHOCYTES; INDUCTION;

D O I：

10.1158/0008-5472.CAN-08-3796

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Immune-mediated tumor rejection relies on fully functional T-cell responses and neutralization of an adverse tumor microenvironment. In clinical trials, we detected peptide-specific but non-tumor-reactive and therefore not fully functional CD8(+) T cells post-vaccination against tumor antigens. Understanding the molecular mechanisms behind nontumor reactivity will he a prerequisite to overcome this CD8(+) T-cell deviation. We report that these non-tumorreactive CD8(+) T cells are characterized by a molecular program associated with hallmarks of "division arrest anergy." Non-tumor-reactive CD8(+) T cells are characterized by coexpression of CD7, CD25, and CD69 as well as elevated levels of lck(p505) and p27(kip1). In vivo quantification revealed high prevalence of non-tumor-reactive CD8(+) T cells with increased levels during cancer vaccination. Furthermore, their presence was associated with a trend toward shorter survival. Dynamics and frequencies of non-target-reactive CD8(+) T cells need to be further addressed in context of therapeutic vaccine development in cancer, chronic infections, and autoimmune diseases. [Cancer Res 2009;69(10):4346-54]

引用

页码：4346 / 4354

页数：9

共 39 条

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