title: Favorable overall survival in stage III melanoma patients after adjuvant dendritic cell vaccination.
abstract: Melanoma patients with regional metastatic disease are at high risk for recurrence and metastatic disease, despite radical lymph node dissection (RLND). We investigated the immunologic response and clinical outcome to adjuvant dendritic cell (DC) vaccination in melanoma patients with regional metastatic disease who underwent RLND with curative intent. In this retrospective study, 78 melanoma patients with regional lymph node metastasis who underwent RLND received autologous DCs loaded with gp100 and tyrosinase and were analyzed for functional tumor-specific T cell responses in skin-test infiltrating lymphocytes. The study shows that adjuvant DC vaccination in melanoma patients with regional lymph node metastasis is safe and induced functional tumor-specific T cell responses in 71% of the patients. The presence of functional tumor-specific T cells was correlated with a better 2-year overall survival (OS) rate. OS was significantly higher after adjuvant DC vaccination compared to 209 matched controls who underwent RLND without adjuvant DC vaccination, 63.6 mo vs. 31.0 mo (p= 0.018; hazard ratio 0.59; 95%CI 0.42-0.84). Five-year survival rate increased from 38% to 53% (p< 0.01). In summary, in melanoma patients with regional metastatic disease, who are at high risk for recurrence and metastatic disease after RLND, adjuvant DC vaccination is well tolerated. It induced functional tumor-specific immune responses in the majority of patients and these were related to clinical outcome. OS was significantly higher compared to matched controls. A randomized clinical trial is needed to prospectively validate the efficacy of DC vaccination in the adjuvant setting.
authors.affiliation: Department of Tumor Immunology; Radboud Institute for Molecular Life Sciences; Radboud University Medical Center; Nijmegen, The Netherlands; Department of Medical Oncology; Radboud University Medical Center; Nijmegen, The Netherlands.
authors.forename: Kalijn F
authors.initials: KF
authors.lastname: Bol
authors.affiliation: Department of Tumor Immunology; Radboud Institute for Molecular Life Sciences; Radboud University Medical Center; Nijmegen, The Netherlands; Department of Medical Oncology; Radboud University Medical Center; Nijmegen, The Netherlands; Department of Radiology and Nuclear Medicine; Radboud University Medical Center; Nijmegen, The Netherlands.
authors.forename: Erik H J G
authors.initials: EH
authors.lastname: Aarntzen
authors.affiliation: Department of Tumor Immunology; Radboud Institute for Molecular Life Sciences; Radboud University Medical Center; Nijmegen, The Netherlands; Department of Surgical Oncology; Radboud University Medical Center; Nijmegen, The Netherlands.
authors.forename: Florentien E M In 't
authors.initials: FE
authors.lastname: Hout
authors.affiliation: Department of Tumor Immunology; Radboud Institute for Molecular Life Sciences; Radboud University Medical Center ; Nijmegen, The Netherlands.
authors.forename: Gerty
authors.initials: G
authors.lastname: Schreibelt
authors.affiliation: Department of Tumor Immunology; Radboud Institute for Molecular Life Sciences; Radboud University Medical Center ; Nijmegen, The Netherlands.
authors.forename: Jeroen H A
authors.initials: JH
authors.lastname: Creemers
authors.affiliation: Department of Tumor Immunology; Radboud Institute for Molecular Life Sciences; Radboud University Medical Center; Nijmegen, The Netherlands; Department of Medicine and Pharmacology; University of Western Australia; Crawley, Australia.
authors.forename: W Joost
authors.initials: WJ
authors.lastname: Lesterhuis
authors.affiliation: Department of Medical Oncology; Radboud University Medical Center ; Nijmegen, The Netherlands.
authors.forename: Winald R
authors.initials: WR
authors.lastname: Gerritsen
authors.affiliation: Department Surgical Oncology; Erasmus MC Cancer Institute ; Rotterdam, The Netherlands.
authors.forename: Dirk J
authors.initials: DJ
authors.lastname: Grunhagen
authors.affiliation: Department Surgical Oncology; Erasmus MC Cancer Institute ; Rotterdam, The Netherlands.
authors.forename: Cornelis
authors.initials: C
authors.lastname: Verhoef
authors.affiliation: Department of Medical Oncology; Academic Medical Center ; Amsterdam, The Netherlands.
authors.forename: Cornelis J A
authors.initials: CJ
authors.lastname: Punt
authors.affiliation: Department of Surgical Oncology; Radboud University Medical Center ; Nijmegen, The Netherlands.
authors.forename: Johannes J
authors.initials: JJ
authors.lastname: Bonenkamp
authors.affiliation: Department of Surgical Oncology; Radboud University Medical Center ; Nijmegen, The Netherlands.
authors.forename: Johannes H W
authors.initials: JH
authors.lastname: de Wilt
authors.affiliation: Department of Tumor Immunology; Radboud Institute for Molecular Life Sciences; Radboud University Medical Center ; Nijmegen, The Netherlands.
authors.forename: Carl G
authors.initials: CG
authors.lastname: Figdor
authors.affiliation: Department of Tumor Immunology; Radboud Institute for Molecular Life Sciences; Radboud University Medical Center; Nijmegen, The Netherlands; Department of Medical Oncology; Radboud University Medical Center; Nijmegen, The Netherlands.
authors.forename: I Jolanda M
authors.initials: IJ
authors.lastname: de Vries
keywords: adjuvant therapy; dendritic cell; immunotherapy; melanoma; vaccination