Cancer vaccine enhanced, non-tumor-reactive CD8(+) T cells exhibit a distinct molecular program associated with "division arrest anergy".
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.
Life and Medical Sciences Bonn, Laboratories for Genomics and Immunoregulation, University of Bonn, Bonn, Germany.
Marc
M
Beyer
Julia
J
Karbach
Michael R
MR
Mallmann
Thomas
T
Zander
Daniela
D
Eggle
Sabine
S
Classen
Svenja
S
Debey-Pascher
Michael
M
Famulok
Elke
E
Jäger
Joachim L
JL
Schultze
D018414:CD8-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology*; D019496:Cancer Vaccines / Q000627:therapeutic use; D002455:Cell Division / Q000276:immunology; D019744:Chemokines, C / Q000235:genetics; D017635:Clonal Anergy / Q000276:immunology*; D020869:Gene Expression Profiling; D015789:HLA-A2 Antigen / Q000276:immunology; D006801:Humans; D016130:Immunophenotyping; D007959:Lymphocyte Culture Test, Mixed; D008212:Lymphocyte Depletion; D009369:Neoplasms / Q000235:genetics* / Q000276:immunology*; D020411:Oligonucleotide Array Sequence Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction
D019496:Cancer Vaccines; D019744:Chemokines, C; D015789:HLA-A2 Antigen; C092390:XCL1 protein, human