[HTML][HTML] Exhaustion of tumor-specific CD8+ T cells in metastases from melanoma patients

L Baitsch, P Baumgaertner, E Devêvre… - The Journal of …, 2011 - Am Soc Clin Investig
L Baitsch, P Baumgaertner, E Devêvre, SK Raghav, A Legat, L Barba, S Wieckowski
The Journal of clinical investigation, 2011Am Soc Clin Investig
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 …
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.
The Journal of Clinical Investigation