Vaccination-induced functional competence of circulating human tumor-specific CD8 T-cells

Int J Cancer. 2012 Jun 1;130(11):2607-17. doi: 10.1002/ijc.26297. Epub 2011 Aug 24.


T-cells specific for foreign (e.g., viral) antigens can give rise to strong protective immune responses, whereas self/tumor antigen-specific T-cells are thought to be less powerful. However, synthetic T-cell vaccines composed of Melan-A/MART-1 peptide, CpG and IFA can induce high frequencies of tumor-specific CD8 T-cells in PBMC of melanoma patients. Here we analyzed the functionality of these T-cells directly ex vivo, by multiparameter flow cytometry. The production of multiple cytokines (IFNγ, TNFα, IL-2) and upregulation of LAMP-1 (CD107a) by tumor (Melan-A/MART-1) specific T-cells was comparable to virus (EBV-BMLF1) specific CD8 T-cells. Furthermore, phosphorylation of STAT1, STAT5 and ERK1/2, and expression of CD3 zeta chain were similar in tumor- and virus-specific T-cells, demonstrating functional signaling pathways. Interestingly, high frequencies of functionally competent T-cells were induced irrespective of patient's age or gender. Finally, CD8 T-cell function correlated with disease-free survival. However, this result is preliminary since the study was a Phase I clinical trial. We conclude that human tumor-specific CD8 T-cells can reach functional competence in vivo, encouraging further development and Phase III trials assessing the clinical efficacy of robust vaccination strategies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antigens, Neoplasm / immunology*
  • CD3 Complex / analysis
  • CD8-Positive T-Lymphocytes / immunology*
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Female
  • Humans
  • Immunocompetence
  • MART-1 Antigen / immunology
  • Male
  • Middle Aged
  • Phosphorylation
  • STAT1 Transcription Factor / metabolism
  • STAT5 Transcription Factor / metabolism
  • Vaccination*


  • Antigens, Neoplasm
  • CD3 Complex
  • CD3 antigen, zeta chain
  • MART-1 Antigen
  • MLANA protein, human
  • STAT1 Transcription Factor
  • STAT1 protein, human
  • STAT5 Transcription Factor
  • Extracellular Signal-Regulated MAP Kinases