Melanocortin 1 Receptor-derived peptides are efficiently recognized by cytotoxic T lymphocytes from melanoma patients

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• 作者：Ferm铆n E. Gonz谩lez ; Marcos Ram铆rez ; Eva B. Allerbring ; Nina Fasching ; Andreas Lundqvist ; Isabel Poschke ; Adnane Achour ; Flavio Salazar-Onfray
• 关键词：Melanoma ; MC1R ; Tumour infiltrating lymphocytes ; Cytotoxic T lymphocytes ; Immunotherapy
• 刊名：Immunobiology
• 出版年：March, 2014
• 年：2014
• 卷：219
• 期：3
• 页码：189-197
• 全文大小：1814 K

文摘

Background

Melanocortin 1 Receptor (MC1R) is expressed in a majority of melanoma biopsies and cell lines. We previously demonstrated that three hydrophobic low-affinity HLA-A2-restricted MC1R-derived peptides: MC1R_291-298, MC1R_244-252 and MC1R_283-291 can elicit cytotoxic T-lymphocytes (CTL) responses from normal donor peripheral blood lymphocytes (PBL). Moreover, peptide-specific CTL recognized a panel of MHC-matched melanomas, demonstrating that human melanoma cell lines naturally present MC1R epitopes. However, the natural presence of MC1R-specific T cells in melanoma patient's tumour and blood remains unknown.

Methods

The presence of anti-MC1R specific CD8⁺ T cells was established in a population of melanoma-specific T cells derived from peripheral blood mononuclear cells (PBMC) and tumour-infiltrating lymphocytes (TIL) from HLA-A2⁺ melanoma patients.

Results

CTLs specific for the three MC1R-derived peptides that lysed allogeneic HLA-A2⁺MC1R⁺ melanomas were elicited from PBMC, demonstrating the existence of an anti-MC1R T cell repertoire in melanoma patients. Moreover, TILs also recognized MC1R epitopes and HLA-A2⁺ melanoma cell lines. Finally, HLA-A2/MC1R₂₄₄-specific CD8⁺ T cell clones derived from TILs and a subset of MC1R₂₉₁ specific TILs were identified using HLA-A2/MC1R tetramers.

Conclusion

Our results demonstrate that MC1R-derived peptides are common immunogenic epitopes for melanoma-specific CTLs and TILs, and may thus be useful for the development of anti-melanoma immunotherapy.