Affiliation:
1. From the Departments of Tumor Immunology, Medical Oncology, Pathology, Radiology, and Dermatology, Radbond University Nijmegen Medical Centre and Nijmegen Centre for Molecular Life Sciences, Nijmegen, the Netherlands
Abstract
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.
Publisher
American Society of Clinical Oncology (ASCO)
Cited by
166 articles.
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