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| Status |
Public on Nov 22, 2011 |
| Title |
Molecular signature of CD8+ T cell exhaustion in metastases but not in peripheral blood from melanoma patients |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
In chronic viral infections such as HIV-1, HBV and HCV, CD8+ T cells may become ”exhausted”, characterized by progressive functional deficiency. Recently, the underlying mechanisms have been characterized by molecular profiling of virus-specific CD8+ T cells. In contrast, only little is known of self/tumor-specific CD8+ T cells from cancer patients, likely because they are much more difficult to assess. For the first time, we determined the molecular profile of human tumor-specific CD8+ T cells, upon sorting of Melan-A/MART-1 specific T cells directly ex vivo from 19 melanoma patients after vaccination with peptide and CpG. For comparison, we sorted protective T cells specific for the two herpes viruses EBV and CMV.
In peripheral blood, we found multiple features of functional effector T cells, with only small but nevertheless significant differences between the three T cell populations, resulting in clean clustering according to antigen specificity. In contrast, Melan-A/MART-1 specific T cells obtained from tumor-infiltrated lymph nodes (TILNs) expressed multiple genes associated with T cell exhaustion, compatible with the known functional deficiencies of T cells in melanoma metastases. We show that individual T cells simultaneously expressed multiple inhibitory receptors implied in functional impairment. Together, the data indicate that in circulation, human tumor-specific T cells have the potential to become competent effector cells. In the tumor environment, however, T cells are exhausted and fail to control malignant disease. Our novel resource data identify mechanisms of functional T cell deficiency in melanoma patients, providing a rational basis for the improvement of immune therapy.
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| Overall design |
52 samples were measured in two sets of experiments. 4 self/tumor-specific samples from blood were replicated between the first and second sets.
Set 1 (32 samples, all from blood): 13 naive samples, 10 EBV-specific samples, 9 self/tumor-specific samples.
Set 2 (20 samples): 7 CMV-specific samples from blood, 7 self/tumor-specific samples from TILN, 6 self/tumor-specific samples from blood.
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| Contributor(s) |
Speiser DE, Baitsch L |
| Citation(s) |
21555851 |
| Submission date |
Oct 05, 2010 |
| Last update date |
Jan 23, 2019 |
| Contact name |
Lukas Baitsch |
| E-mail(s) |
lukas_baitsch@dfci.harvard.edu
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| Organization name |
Dana Farber Cancer Institute
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| Department |
Cancer Biology
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| Lab |
Jean Zhao
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| Street address |
450 Brookline Avenue
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| City |
Boston |
| State/province |
MA |
| ZIP/Postal code |
02215 |
| Country |
USA |
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| Platforms (1) |
| GPL6480 |
Agilent-014850 Whole Human Genome Microarray 4x44K G4112F (Probe Name version) |
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| Samples (52)
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| Relations |
| BioProject |
PRJNA132559 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE24536_RAW.tar |
468.1 Mb |
(http)(custom) |
TAR (of TXT) |
| Processed data included within Sample table |
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