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

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

Onderzoeksoutput: Bijdrage aan tijdschriftArtikelpeer review

20 Citaten (Scopus)

Samenvatting

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.

Originele taal-2Engels
Artikelnummer5097
TijdschriftNature Communications
Volume9
Nummer van het tijdschrift1
DOI's
StatusGepubliceerd - 1 dec. 2018
Extern gepubliceerdJa

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