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 Montpréville, Pierre Validire, Soldano Ferrone, Salem Chouaib, Alexander Eggermont, Jean-Charles Soria, François Lemonnier, Eric Tartour, Nathalie Chaput, Benjamin Besse and Fathia Mami-Chouaib ()
Additional contact information
Aurélie Durgeau: Univ. Paris-Sud, Université Paris-Saclay
Yasemin Virk: Univ. Paris-Sud, Université Paris-Saclay
Gwendoline Gros: Univ. Paris-Sud, Université Paris-Saclay
Elodie Voilin: Univ. Paris-Sud, Université Paris-Saclay
Stéphanie Corgnac: Univ. Paris-Sud, Université Paris-Saclay
Fayçal Djenidi: Univ. Paris-Sud, Université Paris-Saclay
Jérôme Salmon: Univ. Paris-Sud, Université Paris-Saclay
Julien Adam: Univ. Paris-Sud, Université Paris-Saclay
Vincent Montpréville: Univ. Paris-Sud, Université Paris-Saclay
Pierre Validire: Institut Mutualiste Montsouris
Soldano Ferrone: Harvard Medical School
Salem Chouaib: Univ. Paris-Sud, Université Paris-Saclay
Alexander Eggermont: Cancer Institute
Jean-Charles Soria: Gustave Roussy
François Lemonnier: INSERM U1016
Eric Tartour: Service d’Immunologie Biologique
Nathalie Chaput: Laboratory of Immunomonitoring in Oncology, and CNRS-UMS 3655 and INSERM-US23
Benjamin Besse: Gustave Roussy
Fathia Mami-Chouaib: Univ. Paris-Sud, Université Paris-Saclay

Nature Communications, 2018, vol. 9, issue 1, 1-14

Abstract: 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.

Date: 2018
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-018-07603-1 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-07603-1

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-018-07603-1

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().