title: Peptide vaccination in Montanide adjuvant induces and GM-CSF increases CXCR3 and cutaneous lymphocyte antigen expression by tumor antigen-specific CD8 T cells.
abstract: T cell infiltration of melanoma is associated with enhanced clinical efficacy and is a desirable endpoint of immunotherapeutic vaccination. Infiltration is regulated, in part, by chemokine receptors and selectin ligands on the surface of tumor-specific lymphocytes. Therefore, we investigated the expression of two homing molecules--CXCR3 and CLA - on vaccine-induced CD8 T cells, in the context of a clinical trial of a melanoma-specific peptide vaccine. Both CXCR3 and CLA have been associated with T cell infiltration of melanoma. We demonstrate that a single subcutaneous/intradermal administration of peptide vaccine in Montanide adjuvant induces tumor-specific CD8 T cells that are predominantly positive for CXCR3, with a subpopulation of CXCR3(+)CLA(+) cells. Addition of GM-CSF significantly enhances CXCR3 expression and increases the proportion of CLA-expressing cells. Concurrent with CXCR3 and CLA expression, vaccine-induced CD8 cells express high levels of Tbet, IFN-γ, and IL-12Rβ1. Collectively, these studies demonstrate that peptide vaccination in adjuvant induces CD8 T cells with a phenotype that may support infiltration of melanoma.
authors.affiliation: Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Lebanon, NH 03756 ; Norris Cotton Cancer Center, Geisel School of Medicine at Dartmouth, Lebanon, NH 03756.
authors.forename: Eleanor
authors.initials: E
authors.lastname: Clancy-Thompson
authors.affiliation: Department of Microbiology, Immunology, and Cancer Biology, University of Virginia School of Medicine, Charlottesville, VA 22908.
authors.forename: Laura K
authors.initials: LK
authors.lastname: King
authors.affiliation: Department of Microbiology, Immunology, and Cancer Biology, University of Virginia School of Medicine, Charlottesville, VA 22908.
authors.forename: Lenora D
authors.initials: LD
authors.lastname: Nunnley
authors.affiliation: Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Lebanon, NH 03756.
authors.forename: Irene M
authors.initials: IM
authors.lastname: Mullins
authors.affiliation: Department of Surgery, University of Virginia School of Medicine, Charlottesville, VA 22908.
authors.forename: Craig L
authors.initials: CL
authors.lastname: Slingluff
authors.affiliation: Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Lebanon, NH 03756 ; Norris Cotton Cancer Center, Geisel School of Medicine at Dartmouth, Lebanon, NH 03756.
authors.forename: David W
authors.initials: DW
authors.lastname: Mullins
mesh_terms: D000595:Amino Acid Sequence; D000951:Antigens, Neoplasm / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D019496:Cancer Vaccines / Q000008:administration & dosage* / Q000276:immunology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000276:immunology*; D006801:Humans; D008353:Mannitol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000276:immunology; D008545:Melanoma / Q000276:immunology / Q000628:therapy*; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000276:immunology; D009829:Oleic Acids / Q000008:administration & dosage* / Q000276:immunology; D010455:Peptides / Q000008:administration & dosage* / Q000276:immunology; D054367:Receptors, CXCR3 / Q000096:biosynthesis* / Q000276:immunology
chemical_list: D000951:Antigens, Neoplasm; C515187:CXCR3 protein, human; D019496:Cancer Vaccines; D009363:Neoplasm Proteins; D009829:Oleic Acids; D010455:Peptides; D054367:Receptors, CXCR3; C477385:montanide ISA 51; D008353:Mannitol; D016178:Granulocyte-Macrophage Colony-Stimulating Factor
keywords: CLA; CXCR3; GM-CSF; IL-12R; adjuvant; melanoma; peptide vaccines