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.
Beyer
Marc
M
Life and Medical Sciences Bonn, Laboratories for Genomics and Immunoregulation, University of Bonn, Bonn, Germany.
Karbach
Julia
J
Mallmann
Michael R
MR
Zander
Thomas
T
Eggle
Daniela
D
Classen
Sabine
S
Debey-Pascher
Svenja
S
Famulok
Michael
M
Jäger
Elke
E
Schultze
Joachim L
JL
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