Induction of protective antitumor immunity through attenuation of ERAAP function


James, E., Bailey, I., Sugiyarto, G. and Elliott, T. (2013) Induction of protective antitumor immunity through attenuation of ERAAP function Journal of Immunology, 190, (11), pp. 5839-5846. (doi:10.4049/jimmunol.1300220). (PMID:23610143).

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Description/Abstract

The endoplasmic reticulum aminopeptidase associated with Ag processing, ERAAP, plays an important role in the trimming of antigenic peptides for presentation at the cell surface complexed with MHC class I molecules. Tumors express varying levels of ERAAP, highlighting a possible mechanism of immune-evasion through alteration of the peptide repertoire. Using the CT26 tumor model, we investigated the effects of ERAAP modulation on peptide presentation and the use of ERAAP inhibition as an antitumor therapy. We show that generation of the cross-protective tumor Ag GSW11 in the colorectal carcinoma CT26 is increased when ERAAP expression is reduced. BALB/c mice with reduced ERAAP expression challenged with CT26 induced protective immunity that was mediated by CD8+ T cells. This antitumor immunity also protected mice when rechallenged with wild-type CT26 tumor; strong CD8+ T cell responses to GSW11 were observed, despite its presentation being considerably lower. Furthermore, boosting the tumor immunogenicity through inhibition of ERAAP function with the small molecule inhibitor leucinethiol in vitro, or in established tumors in vivo, abrogated tumor growth and prolonged survival. Thus, our results highlight the promising possibility of using modulation of ERAAP to generate protective antitumor responses as a strategy for cancer immunotherapy.

Item Type: Article
Digital Object Identifier (DOI): doi:10.4049/jimmunol.1300220
ISSNs: 0022-1767 (print)
Related URLs:
Subjects: R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Organisations: Cancer Sciences
ePrint ID: 351996
Date :
Date Event
22 April 2013Published
Date Deposited: 30 Apr 2013 12:03
Last Modified: 17 Apr 2017 15:36
Further Information:Google Scholar
URI: http://eprints.soton.ac.uk/id/eprint/351996

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