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

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Version: Final published version
Serval ID
serval:BIB_9E5EBEDCC14D
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Exhaustion of tumor-specific CD8⁺ T cells in metastases from melanoma patients.
Journal
Journal of Clinical Investigation
Author(s)
Baitsch L., Baumgaertner P., Devêvre E., Raghav S.K., Legat A., Barba L., Wieckowski S., Bouzourene H., Deplancke B., Romero P., Rufer N., Speiser D.E.
ISSN
1558-8238 (Electronic)
ISSN-L
0021-9738
Publication state
Published
Issued date
2011
Volume
121
Number
6
Pages
2350-2360
Language
english
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.
Keywords
CD8-Positive T-Lymphocytes/immunology, CD8-Positive T-Lymphocytes/metabolism, Cancer Vaccines/immunology, Cancer Vaccines/therapeutic use, CpG Islands/immunology, Cytomegalovirus/immunology, Cytomegalovirus Infections/immunology, Epstein-Barr Virus Infections/immunology, Gene Expression Profiling, Herpesvirus 4, Human/immunology, Humans, Lymphocytes, Tumor-Infiltrating/immunology, MART-1 Antigen/immunology, Melanoma/immunology, Melanoma/secondary, Molecular Sequence Data, Receptors, Immunologic/biosynthesis, Receptors, Immunologic/genetics, T-Cell Antigen Receptor Specificity, T-Lymphocyte Subsets/immunology, T-Lymphocyte Subsets/metabolism, Vaccination, Virus Latency/immunology
Pubmed
Web of science
Open Access
Yes
Create date
13/01/2012 15:45
Last modification date
20/08/2019 15:04
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