Adjuvant dendritic cell vaccination induces tumor-specific immune responses in the majority of stage III melanoma patients.
Loading...
Embargo End Date
ICR Authors
Authors
Boudewijns, S
Bol, KF
Schreibelt, G
Westdorp, H
Textor, JC
van Rossum, MM
Scharenborg, NM
de Boer, AJ
van de Rakt, MWMM
Pots, JM
van Oorschot, TGM
Duiveman-de Boer, T
Olde Nordkamp, MA
van Meeteren, WSEC
van der Graaf, WTA
Bonenkamp, JJ
de Wilt, JHW
Aarntzen, EHJG
Punt, CJA
Gerritsen, WR
Figdor, CG
de Vries, IJM
Bol, KF
Schreibelt, G
Westdorp, H
Textor, JC
van Rossum, MM
Scharenborg, NM
de Boer, AJ
van de Rakt, MWMM
Pots, JM
van Oorschot, TGM
Duiveman-de Boer, T
Olde Nordkamp, MA
van Meeteren, WSEC
van der Graaf, WTA
Bonenkamp, JJ
de Wilt, JHW
Aarntzen, EHJG
Punt, CJA
Gerritsen, WR
Figdor, CG
de Vries, IJM
Document Type
Journal Article
Date
2016-07
Date Accepted
2016-05-15
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.
Citation
Oncoimmunology, 2016, 5 (7), pp. e1191732 - ?
Source Title
Publisher
ISSN
2162-4011
eISSN
2162-402X
Collections
Research Team
Clinical and Translational Sarcoma