期刊
JOURNAL OF CLINICAL INVESTIGATION
卷 121, 期 6, 页码 2350-2360出版社
AMER SOC CLINICAL INVESTIGATION INC
DOI: 10.1172/JCI46102
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资金
- Ludwig Institute for Cancer Research
- Cancer Research Institute (USA)
- Cancer Vaccine Collaborative
- Atlantic Philanthropies (USA)
- Wilhelm Sander-Foundation (Germany)
- Swiss Cancer League [02279-08-2008]
- Swiss National Science Foundation
- Swiss National Center of Competence in Research (NCCR) Molecular Oncology
In chronic viral infections, CD8(+) T cells become functionally deficient and display multiple molecular alterations. In contrast, only little is known of self- and tumor-specific CD8(+) T cells from mice and humans. Here we determined molecular profiles of tumor-specific CD8(+) T cells from melanoma patients. In peripheral blood from patients vaccinated with CpG and the melanoma antigen Melan-A/MART-1 peptide, we found functional effector T cell populations, with only small but nevertheless significant differences in T cells specific for persistent herpesviruses (EBV and CMV). In contrast, Melan-A/MART-1-specific T cells isolated from metastases from patients with melanoma expressed a large variety of genes associated with T cell exhaustion. The identified exhaustion profile revealed extended molecular alterations. Our data demonstrate a remarkable coexistence of effector cells in circulation and exhausted cells in the tumor environment. Functional T cell impairment is mediated by inhibitory receptors and further molecular pathways, which represent potential targets for cancer therapy.
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