Immunomonitoring tumor-specific T cells in delayed-type hypersensitivity skin biopsies after dendritic cell vaccination correlates with clinical outcome.
SourceJournal of Clinical Oncology, 23, 24, (2005), pp. 5779-5787
Article / Letter to editor
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Journal of Clinical Oncology
SubjectDCN 2: Functional Neurogenomics; DCN 3: Neuroinformatics; N4i 1: Pathogenesis and modulation of inflammation; NCMLS 1: Immunity, infection and tissue repair; NCMLS 2: Immune Regulation; ONCOL 1: Hereditary cancer and cancer-related syndromes; ONCOL 3: Translational research; UMCN 1.4: Immunotherapy, gene therapy and transplantation; UMCN 1.5: Interventional oncology
PURPOSE: 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. PATIENTS AND 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). CONCLUSION: These findings demonstrate the potency of this novel approach in the monitoring of vaccination studies in cancer patients.
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