1. Adjuvant dendritic cell vaccination induces tumor-specific immune responses in the majority of stage III melanoma patients
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Nicole M. Scharenborg, Michelle M. van Rossum, Tjitske Duiveman-de Boer, Harm Westdorp, Michel A.M. Olde Nordkamp, Gerty Schreibelt, Tom G. M. van Oorschot, I. Jolanda M. de Vries, Annemiek J. de Boer, Mandy W.M.M. van de Rakt, Steve Boudewijns, Johannes H. W. de Wilt, Johannes J. Bonenkamp, Jeanne M. Pots, Erik H.J.G. Aarntzen, Carl G. Figdor, Kalijn F. Bol, Winald R. Gerritsen, Cornelis J. A. Punt, Winette T. A. van der Graaf, Wilmy S. E. C. van Meeteren, Johannes Textor, Cancer Center Amsterdam, and Oncology
- Subjects
0301 basic medicine ,medicine.medical_treatment ,T cell ,Cancer development and immune defence Radboud Institute for Molecular Life Sciences [Radboudumc 2] ,Immunology ,immune response ,03 medical and health sciences ,Tumours of the digestive tract Radboud Institute for Health Sciences [Radboudumc 14] ,Cancer development and immune defence Radboud Institute for Health Sciences [Radboudumc 2] ,0302 clinical medicine ,Immune system ,Antigen ,Tumours of the digestive tract Radboud Institute for Molecular Life Sciences [Radboudumc 14] ,Immunology and Allergy ,Medicine ,Stage IIIC ,Original Research ,business.industry ,Radical Lymph Node Dissection ,Dendritic cell ,DTH ,vaccination ,030104 developmental biology ,medicine.anatomical_structure ,Oncology ,030220 oncology & carcinogenesis ,Urological cancers Radboud Institute for Health Sciences [Radboudumc 15] ,stage III melanoma ,skin-infiltrating lymphocytes ,business ,Adjuvant ,CD8 ,Rare cancers Radboud Institute for Health Sciences [Radboudumc 9] - Abstract
Contains fulltext : 170905.pdf (Publisher’s version ) (Open Access) 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.
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- 2016
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