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J Clin Invest. 2011 Jun;121(6):2350-60. doi: 10.1172/JCI46102. Epub 2011 May 9.

Exhaustion of tumor-specific CD8⁺ T cells in metastases from melanoma patients.

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1
Clinical Tumor Immune-Biology Unit, Ludwig Institute for Cancer Research, Lausanne, Switzerland.

Abstract

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.

PMID:
21555851
PMCID:
PMC3104769
DOI:
10.1172/JCI46102
[Indexed for MEDLINE]
Free PMC Article
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