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Oncoimmunology. 2016 May 31;5(7):e1191732. doi: 10.1080/2162402X.2016.1191732. eCollection 2016 Jul.

Adjuvant dendritic cell vaccination induces tumor-specific immune responses in the majority of stage III melanoma patients.

Author information

1
Department of Medical Oncology, Radboud University Medical Center Nijmegen, Nijmegen, the Netherlands; Department of Tumor Immunology, Radboud University Medical Center, Radboud Institute for Molecular Life Sciences, Nijmegen, the Netherlands.
2
Department of Tumor Immunology, Radboud University Medical Center, Radboud Institute for Molecular Life Sciences , Nijmegen, the Netherlands.
3
Department of Dermatology, Radboud University Medical Center , Nijmegen, the Netherlands.
4
Department of Medical Oncology, Radboud University Medical Center Nijmegen, Nijmegen, the Netherlands; The Institute of Cancer Research and the Royal Marsden NHS Foundation Trust, London, United Kingdom.
5
Department of Surgical Oncology, Radboud University Medical Center , Nijmegen, the Netherlands.
6
Department of Tumor Immunology, Radboud University Medical Center, Radboud Institute for Molecular Life Sciences, Nijmegen, the Netherlands; Department of Radiology and Nuclear Medicine, Radboud University Medical Center, Nijmegen, the Netherlands.
7
Department of Medical Oncology, Academic Medical Center , Amsterdam, the Netherlands.
8
Department of Medical Oncology, Radboud University Medical Center Nijmegen , Nijmegen, the Netherlands.

Abstract

PURPOSE:

To determine the effectiveness of adjuvant dendritic cell (DC) vaccination to induce tumor-specific immunological responses in stage III melanoma patients.

EXPERIMENTAL DESIGN:

Retrospective analysis of stage III melanoma patients, vaccinated with autologous monocyte-derived DC loaded with tumor-associated antigens (TAA) gp100 and tyrosinase after radical lymph node dissection. Skin-test infiltrating lymphocytes (SKILs) obtained from delayed-type hypersensitivity skin-test biopsies were analyzed for the presence of TAA-specific CD8(+) T cells by tetrameric MHC-peptide complexes and by functional TAA-specific T cell assays, defined by peptide-recognition (T2 cells) and/or tumor-recognition (BLM and/or MEL624) with specific production of Th1 cytokines and no Th2 cytokines.

RESULTS:

Ninety-seven patients were analyzed: 21 with stage IIIA, 34 with stage IIIB, and 42 had stage IIIC disease. Tetramer-positive CD8(+) T cells were present in 68 patients (70%), and 24 of them showed a response against all 3 epitopes tested (gp100:154-162, gp100:280-288, and tyrosinase:369-377) at any point during vaccinations. A functional T cell response was found in 62 patients (64%). Rates of peptide-recognition of gp100:154-162, gp100:280-288, and tyrosinase:369-377 were 40%, 29%, and 45%, respectively. Median recurrence-free survival and distant metastasis-free survival of the whole study population were 23.0 mo and 36.8 mo, respectively.

CONCLUSIONS:

DC vaccination induces a functional TAA-specific T cell response in the majority of stage III melanoma patients, indicating it is more effective in stage III than in stage IV melanoma patients. Furthermore, performing multiple cycles of vaccinations enhances the chance of a broader immune response.

KEYWORDS:

DTH; Dendritic cell; immune response; skin-infiltrating lymphocytes; stage III melanoma; vaccination

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