Article open access publication

Broadening the repertoire of melanoma-associated T-cell epitopes

Cancer Immunology, Immunotherapy, Springer Nature, ISSN 1432-0851

Volume 64, 5, 2015

DOI:10.1007/s00262-015-1664-x, Dimensions: pub.1038617413, PMC: PMC4412285, PMID: 25854582,

Authors

Frøsig, Thomas Morch (1) (2) (3)
Lyngaa, Rikke (2) (3)
Met, Özcan (2) (4)
Donia, Marco (2) (4)
Hadrup, Sine Reker * (2) (3)

* Corresponding author

Affiliations

Organisations

  1. (1) University of Copenhagen, grid.5254.6, KU
  2. (2) Herlev Hospital, grid.411900.d, Capital Region
  3. (3) Technical University of Denmark, grid.5170.3, DTU
  4. (4) Copenhagen University Hospital, grid.4973.9, Capital Region

Countries

Denmark

Continents

Europe

Description

Immune therapy has provided a significant breakthrough in the treatment of metastatic melanoma. Despite the remarkable clinical efficacy and established involvement of effector CD8 T cells, the knowledge of the exact peptide-MHC complexes recognized by T cells on the tumor cell surface is limited. Many melanoma-associated T-cell epitopes have been described, but this knowledge remains largely restricted to HLA-A2, and we lack understanding of the T-cell recognition in the context of other HLA molecules. We selected six melanoma-associated antigens (MAGE-A3, NY-ESO-1, gp100, Mart1, tyrosinase and TRP-2) that are frequently recognized in patients with the aim of identifying novel T-cell epitopes restricted to HLA-A1, -A3, -A11 and -B7. Using in silico prediction and in vitro confirmation, we identified 127 MHC ligands and analyzed the T-cell responses against these ligands via the MHC multimer-based enrichment of peripheral blood from 39 melanoma patients and 10 healthy donors. To dissect the T-cell reactivity against this large peptide library, we used combinatorial-encoded MHC multimers and observed the T-cell responses against 17 different peptide-MHC complexes in the patient group and four in the healthy donor group. We confirmed the processing and presentation of HLA-A3-restricted T-cell epitopes from tyrosinase (TQYESGSMDK) and gp100 (LIYRRRLMK) and an HLA-A11-restricted T-cell epitope from gp100 (AVGATKVPR) via the cytolytic T-cell recognition of melanoma cell lines and/or K562 cells expressing the appropriate antigen and HLA molecule. We further found T-cell reactivity against two of the identified sequences among tumor-infiltrating lymphocytes from melanoma patients, suggesting a potential clinical relevance of these sequences.

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University of Copenhagen

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Danish Open Access Indicator

2015: Realized

Research area: Medicine

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2015: Level 1

Research area: Medicine

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Times Cited: 8

Field Citation Ratio (FCR): 1.32

Relative Citation ratio (RCR): 0.39

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