Induced pluripotent stem cells display a distinct set of MHC I-associated peptides shared by human cancers.
CP: stem cell research
cancer immunotherapy
induced pluripotent stem cells
major histocompatibility complex class I
mass spectrometry
tumor-specific antigens
Journal
Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691
Informations de publication
Date de publication:
16 08 2022
16 08 2022
Historique:
received:
02
08
2021
revised:
20
06
2022
accepted:
27
07
2022
entrez:
17
8
2022
pubmed:
18
8
2022
medline:
20
8
2022
Statut:
ppublish
Résumé
Previous reports showed that mouse vaccination with pluripotent stem cells (PSCs) induces durable anti-tumor immune responses via T cell recognition of some elusive oncofetal epitopes. We characterize the MHC I-associated peptide (MAP) repertoire of human induced PSCs (iPSCs) using proteogenomics. Our analyses reveal a set of 46 pluripotency-associated MAPs (paMAPs) absent from the transcriptome of normal tissues and adult stem cells but expressed in PSCs and multiple adult cancers. These paMAPs derive from coding and allegedly non-coding (48%) transcripts involved in pluripotency maintenance, and their expression in The Cancer Genome Atlas samples correlates with source gene hypomethylation and genomic aberrations common across cancer types. We find that several of these paMAPs were immunogenic. However, paMAP expression in tumors coincides with activation of pathways instrumental in immune evasion (WNT, TGF-β, and CDK4/6). We propose that currently available inhibitors of these pathways could synergize with immune targeting of paMAPs for the treatment of poorly differentiated cancers.
Identifiants
pubmed: 35977509
pii: S2211-1247(22)01058-0
doi: 10.1016/j.celrep.2022.111241
pii:
doi:
Substances chimiques
Histocompatibility Antigens Class I
0
Peptides
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
111241Subventions
Organisme : CIHR
ID : FDN 148400
Pays : Canada
Organisme : CIHR
ID : FRN 159925
Pays : Canada
Informations de copyright
Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests A.A., M.-P.H., P.T., and C.P. are named inventors on a patent application filed by Université de Montréal and covering antigens described in this article.