mart-1-antigen and Cytomegalovirus-Infections

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.

Topics: Cancer Vaccines; CD8-Positive T-Lymphocytes; CpG Islands; Cytomegalovirus; Cytomegalovirus Infections; Epstein-Barr Virus Infections; Gene Expression Profiling; Herpesvirus 4, Human; Humans; Lymphocytes, Tumor-Infiltrating; MART-1 Antigen; Melanoma; Molecular Sequence Data; Receptors, Immunologic; T-Cell Antigen Receptor Specificity; T-Lymphocyte Subsets; Vaccination; Virus Latency