AIRE polymorphism, melanoma antigen-specific T cell immunity, and susceptibility to melanoma

[en] AIRE is involved in susceptibility to melanoma perhaps regulating T cell immunity against melanoma antigens (MA). To address this issue, AIRE and MAGEB2 expressions were measured by real time PCR in medullary thymic epithelial cells (mTECs) from two strains of C57BL/6 mice bearing either T or C allelic variant of the rs1800522 AIRE SNP. Moreover, the extent of apoptosis induced by mTECs in MAGEB2-specific T cells and the susceptibility to in vivo melanoma B16F10 cell challenge were compared in the two mouse strains. The C allelic variant, protective in humans against melanoma, induced lower AIRE and MAGEB2 expression in C57BL/6 mouse mTECs than the T allele. Moreover, mTECs expressing the C allelic variant induced lower extent of apoptosis in MAGEB2-specific syngeneic T cells than mTECs bearing the T allelic variant (p < 0.05). Vaccination against MAGEB2 induced higher frequency of MAGEB2-specific CTL and exerted higher protective effect against melanoma development in mice bearing the CC AIRE genotype than in those bearing the TT one (p < 0.05). These findings show that allelic variants of one AIRE SNP may differentially shape the MA-specific T cell repertoire potentially influencing susceptibility to melanoma.

Research Center/Unit :

CEBR, Centre of Excellence for Biomedical Research

Disciplines :

Oncology

Author, co-author :

Conteduca, Giuseppina ; Université de Liège > GIGA-R : Hématologie

Language :

English

Title :

AIRE polymorphism, melanoma antigen-specific T cell immunity, and susceptibility to melanoma

Publication date :

22 August 2016

Journal title :

Oncotarget

eISSN :

1949-2553

Publisher :

Impact Journals, Albany, United States - New York

Peer reviewed :

Peer Reviewed verified by ORBi

Name of the research project :

Immunotherapy anti tumoral

Funders :

MIUR - Ministero dell'Istruzione, dell'Università e della Ricerca
AIRC - Associazione Italiana per la Ricerca sul Cancro

Funding number :

PRIN, grant from MIUR

Available on ORBi :

since 21 November 2016

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