期刊
INTERNATIONAL JOURNAL OF CANCER
卷 130, 期 11, 页码 2607-2617出版社
WILEY
DOI: 10.1002/ijc.26297
关键词
CD8 T-cell effector function; vaccination; CpG oligodeoxynucleotides; Melan-A; MART-1 peptide; melanoma
类别
资金
- Swiss Cancer League/Oncosuisse [02279-08-2008]
- Ludwig Institute for Cancer Research
- Cancer Research Institute (USA)
- Cancer Vaccine Collaborative, Atlantic Philanthropies (USA)
- Wilhelm Sander-Foundation (Germany)
- Swiss National Science Foundation
- Swiss National Center of Competence in Research (NCCR) Molecular Oncology
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 (IFN?, TNFa, 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.
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