Induced pluripotent stem cells display a distinct set of MHC I-associated peptides shared by human cancers

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-b, 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.,

Publication
Cell Reports
Mathieu Courcelles
Mathieu Courcelles
Étudiant au doctorat en bio-informatique (2008-2012 avec Pierre Thibault, IRIC)
Sébastien Lemieux
Sébastien Lemieux
Chercheur principal

Chercheur principal, Unité de recherche en bio-informatique fonctionnelle et structurale, IRIC | Direction scientifique de la plateforme de Bio-informatique | Professeur agrégé, Département de biochimie et médecine moléculaire, Université de Montréal