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Immunomonitoring Tumor-Specific T Cells in Delayed-Type Hypersensitivity Skin Biopsies After Dendritic Cell Vaccination Correlates With Clinical Outcome

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

Address reprint requests to Gosse J. Adema, PhD, Department of Tumor Immunology, University Medical Center Nijmegen, Geert Grooteplein 26-28, 6500 HB Nijmegen, the Netherlands; e-mail: g.adema{at}ncmls.ru.nl

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.

C.J.A.P and G.J.A. contributed equally to this study.

Authors' disclosures of potential conflicts of interest are found at the end of this article.

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