title: Exhaustion of tumor-specific CD8⁺ T cells in metastases from melanoma patients.
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.
authors.affiliation: Clinical Tumor Immune-Biology Unit, Ludwig Institute for Cancer Research, Lausanne, Switzerland.
authors.forename: Lukas
authors.initials: L
authors.lastname: Baitsch
authors.forename: Petra
authors.initials: P
authors.lastname: Baumgaertner
authors.forename: Estelle
authors.initials: E
authors.lastname: Devêvre
authors.forename: Sunil K
authors.initials: SK
authors.lastname: Raghav
authors.forename: Amandine
authors.initials: A
authors.lastname: Legat
authors.forename: Leticia
authors.initials: L
authors.lastname: Barba
authors.forename: Sébastien
authors.initials: S
authors.lastname: Wieckowski
authors.forename: Hanifa
authors.initials: H
authors.lastname: Bouzourene
authors.forename: Bart
authors.initials: B
authors.lastname: Deplancke
authors.forename: Pedro
authors.initials: P
authors.lastname: Romero
authors.forename: Nathalie
authors.initials: N
authors.lastname: Rufer
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Speiser
mesh_terms: D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D019496:Cancer Vaccines / Q000276:immunology / Q000627:therapeutic use; D018899:CpG Islands / Q000276:immunology*; D003587:Cytomegalovirus / Q000276:immunology; D003586:Cytomegalovirus Infections / Q000276:immunology; D020031:Epstein-Barr Virus Infections / Q000276:immunology; D020869:Gene Expression Profiling; D004854:Herpesvirus 4, Human / Q000276:immunology; D006801:Humans; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology; D058965:MART-1 Antigen / Q000276:immunology*; D008545:Melanoma / Q000276:immunology* / Q000556:secondary* / Q000628:therapy; D008969:Molecular Sequence Data; D011971:Receptors, Immunologic / Q000096:biosynthesis / Q000235:genetics; D037182:T-Cell Antigen Receptor Specificity; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D014611:Vaccination; D017735:Virus Latency / Q000276:immunology
chemical_list: D019496:Cancer Vaccines; D058965:MART-1 Antigen; C548667:MLANA protein, human; D011971:Receptors, Immunologic