title: Immunomonitoring tumor-specific T cells in delayed-type hypersensitivity skin biopsies after dendritic cell vaccination correlates with clinical outcome.
abstract: OBJECTIVE
  Tumor-specific immunomonitoring is essential to evaluate the efficacy of vaccination against cancer. In this study, we investigated the predictive value of the presence or absence of antigen-specific T cells in biopsies from delayed-type hypersensitivity (DTH) sites.
  
  
  METHODS
  In our ongoing clinical trials, HLA-A2.1+ melanoma patients were vaccinated with mature dendritic cells (DC) pulsed with melanoma-associated peptides (gp100 and tyrosinase) and keyhole limpet hemocyanin.
  
  
  RESULTS
  After intradermal administration of a DTH challenge with gp100- and tyrosinase peptide-loaded DC, essentially all patients showed a positive induration. In clinically responding patients, T cells specific for the antigen preferentially accumulated in the DTH site, as visualized by in situ tetramer staining. Furthermore, significant numbers of functional gp100 and tyrosinase tetramer-positive T cells could be isolated from these DTH biopsies, in accordance with the applied antigen in the DTH challenge. We observed a direct correlation between the presence of DC vaccine-related T cells in the DTH biopsies of stage IV melanoma patients and a positive clinical outcome (P = .0012).
  
  
  CONCLUSIONS
  These findings demonstrate the potency of this novel approach in the monitoring of vaccination studies in cancer patients.
authors.affiliation: Department of Tumor Immunology, Radbond University Nijmegen Medical Center, Geert Grooteplein 26-28, 6500 HB Nijmegen, Netherlands.
authors.forename: I Jolanda M
authors.initials: IJ
authors.lastname: de Vries
authors.forename: Monique R
authors.initials: MR
authors.lastname: Bernsen
authors.forename: W Joost
authors.initials: WJ
authors.lastname: Lesterhuis
authors.forename: Nicole M
authors.initials: NM
authors.lastname: Scharenborg
authors.forename: Simon P
authors.initials: SP
authors.lastname: Strijk
authors.forename: Marie-Jeanne P
authors.initials: MJ
authors.lastname: Gerritsen
authors.forename: Dirk J
authors.initials: DJ
authors.lastname: Ruiter
authors.forename: Carl G
authors.initials: CG
authors.lastname: Figdor
authors.forename: Cornelis J A
authors.initials: CJ
authors.lastname: Punt
authors.forename: Gosse J
authors.initials: GJ
authors.lastname: Adema
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology; D001706:Biopsy; D019496:Cancer Vaccines / Q000627:therapeutic use*; D003713:Dendritic Cells / Q000276:immunology*; D005434:Flow Cytometry; D006433:Hemocyanins / Q000494:pharmacology; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000276:immunology*; D008545:Melanoma / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D008562:Membrane Glycoproteins / Q000494:pharmacology; D014442:Monophenol Monooxygenase / Q000494:pharmacology; D009363:Neoplasm Proteins / Q000494:pharmacology; D011237:Predictive Value of Tests; D012878:Skin Neoplasms / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014611:Vaccination; D058951:gp100 Melanoma Antigen
chemical_list: D000276:Adjuvants, Immunologic; D019496:Cancer Vaccines; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; C548637:PMEL protein, human; D058951:gp100 Melanoma Antigen; D006433:Hemocyanins; D014442:Monophenol Monooxygenase; C032808:keyhole-limpet hemocyanin