Characterization of antigen-specific CD8+ T lymphocyte responses in skin and peripheral blood following intradermal peptide vaccination

• Published in: Cancer immunity Vol. 5; p. 5
• Main Authors: Chen, Qiyuan, Jackson, Heather, Shackleton, Mark, Parente, Phillip, Hopkins, Wendie, Sturrock, Sue, MacGregor, Duncan, Maraskovsky, Eugene, Tai, Tsin Yee, Dimopoulos, Nektaria, Masterman, Kelly-Anne, Luke, Tina, Davis, Ian D, Chen, Weisan, Cebon, Jonathan
• Format: Journal Article
• Language: English
• Published: United States 09.03.2005
• Subjects: Antigens, Neoplasm - immunology; Blood Cells - immunology; Cancer Vaccines - administration & dosage; Cancer Vaccines - immunology; CD4-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - immunology; Cell Line, Tumor; Cytotoxicity Tests, Immunologic; Humans; Hypersensitivity, Delayed - immunology; Injections, Intradermal; Interferon-gamma - biosynthesis; Lymphocytes, Tumor-Infiltrating - immunology; Melanoma - immunology; Skin - immunology; Skin Neoplasms - immunology; Vaccines, Subunit - administration & dosage; Vaccines, Subunit - immunology
• ISSN: 1424-9634

Immune responses to cancer vaccines are commonly tested by measuring cutaneous reactions to intradermal (i.d.) antigen. When well-characterized peptide epitopes are injected i.d., infiltrates of CD4+ and CD8+ T lymphocytes are frequently seen. In this study, we have further characterized T cells derived from vaccine-infiltrating lymphocyte (VIL) responses. We found that the infiltrates capable of producing IFN-gamma and cytolytic activity could recognize vaccine peptide, as well as antigen-positive melanoma cells. We studied antigen-specific T cell responses from VILs and peripheral blood in 10 patients who participated in a clinical trial. All patients received systemic Flt3 ligand (20 microg/kg/d) and i.d. peptides: Three NY-ESO-1 peptides, SLLMWITQCFL (157-167), SLLMWITQC (157-165), QLSLLMWIT (155-163); tyrosinase internal peptide YMDGTMSQV (368-376); Melan-A/MART-1 analogue peptide ELAGIGILTV (26-35, E27L substitution); and influenza matrix peptide GILGFVFTL (58-66). In 54 paired VIL and peripheral blood analyses, a good correlation was found between responses in skin and in blood. These cells could be rapidly expanded in a short-term assay and thus appear to be memory T cells. The demonstrated presence of antigen-specific T cells at vaccination sites validates this method of assessing the immune response to i.d. vaccines.