Immunomonitoring tumor-specific T cells in delayed-type hypersensitivity skin biopsies after dendritic cell vaccination correlates with clinical outcome.
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.
de Vries
I Jolanda M
IJ
Department of Tumor Immunology, Radbond University Nijmegen Medical Center, Geert Grooteplein 26-28, 6500 HB Nijmegen, Netherlands.
Bernsen
Monique R
MR
Lesterhuis
W Joost
WJ
Scharenborg
Nicole M
NM
Strijk
Simon P
SP
Gerritsen
Marie-Jeanne P
MJ
Ruiter
Dirk J
DJ
Figdor
Carl G
CG
Punt
Cornelis J A
CJ
Adema
Gosse J
GJ
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
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