Human preprocalcitonin self-antigen generates TAP-dependent and -independent epitopes triggering optimised T-cell responses toward immune-escaped tumours View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2018-12

AUTHORS

Aurélie Durgeau, Yasemin Virk, Gwendoline Gros, Elodie Voilin, Stéphanie Corgnac, Fayçal Djenidi, Jérôme Salmon, Julien Adam, Vincent de Montpréville, Pierre Validire, Soldano Ferrone, Salem Chouaib, Alexander Eggermont, Jean-Charles Soria, François Lemonnier, Eric Tartour, Nathalie Chaput, Benjamin Besse, Fathia Mami-Chouaib

ABSTRACT

Tumours often evade CD8 T-cell immunity by downregulating TAP. T-cell epitopes associated with impaired peptide processing are immunogenic non-mutated neoantigens that emerge during tumour immune evasion. The preprocalcitonin (ppCT)16-25 neoepitope belongs to this category of antigens. Here we show that most human lung tumours display altered expression of TAP and frequently express ppCT self-antigen. We also show that ppCT includes HLA-A2-restricted epitopes that are processed by TAP-independent and -dependent pathways. Processing occurs in either the endoplasmic reticulum, by signal peptidase and signal peptide peptidase, or in the cytosol after release of a signal peptide precursor or retrotranslocation of a procalcitonin substrate by endoplasmic-reticulum-associated degradation. Remarkably, ppCT peptide-based immunotherapy induces efficient T-cell responses toward antigen processing and presenting machinery-impaired tumours transplanted into HLA-A*0201-transgenic mice and in NOD-scid-Il2rγnull mice adoptively transferred with human PBMC. Thus, ppCT-specific T lymphocytes are promising effectors for treatment of tumours that have escaped immune recognition. More... »

PAGES

5097

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/s41467-018-07603-1

DOI

http://dx.doi.org/10.1038/s41467-018-07603-1

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1110204835

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/30504837


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