Immunomonitoring tumor-specific T cells in delayed-type hypersensitivity skin biopsies after dendritic cell vaccination correlates with clinical outcome
I Jolanda M de Vries, Monique R Bernsen, W Joost Lesterhuis, Nicole M Scharenborg, Simon P Strijk, Marie-Jeanne P Gerritsen, Dirk J Ruiter, Carl G Figdor, Cornelis J A Punt, Gosse J Adema, I Jolanda M de Vries, Monique R Bernsen, W Joost Lesterhuis, Nicole M Scharenborg, Simon P Strijk, Marie-Jeanne P Gerritsen, Dirk J Ruiter, Carl G Figdor, Cornelis J A Punt, Gosse J Adema
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.
Source: PubMed