1. Cancer vaccine enhanced, non-tumor-reactive CD8(+) T cells exhibit a distinct molecular program associated with "division arrest anergy".
- Author
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Beyer M, Karbach J, Mallmann MR, Zander T, Eggle D, Classen S, Debey-Pascher S, Famulok M, Jäger E, and Schultze JL
- Subjects
- Cancer Vaccines therapeutic use, Cell Division immunology, Chemokines, C genetics, Gene Expression Profiling, HLA-A2 Antigen immunology, Humans, Immunophenotyping, Lymphocyte Culture Test, Mixed, Lymphocyte Depletion, Oligonucleotide Array Sequence Analysis, Reverse Transcriptase Polymerase Chain Reaction, CD8-Positive T-Lymphocytes cytology, CD8-Positive T-Lymphocytes immunology, Clonal Anergy immunology, Neoplasms genetics, Neoplasms immunology
- Abstract
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 be a prerequisite to overcome this CD8(+) T-cell deviation. We report that these non-tumor-reactive 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.
- Published
- 2009
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