Publication — IRIC

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

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.

Publication date
août 16, 2022
Principal Investigators
Apavaloaei A, Hesnard L, Hardy MP, Benabdallah B, Ehx G, Thériault C, Laverdure JP, Durette C, Lanoix J, Courcelles M, Noronha N, Chauhan KD, Lemieux S, Beauséjour C, Bhatia M, Thibault P, Perreault C
PubMed reference
Cell Rep 2022;40(7):111241
PubMed ID
35977509
Affiliation
Institute for Research in Immunology and Cancer (IRIC), University of Montreal, Montreal, QC H3T 1J4, Canada; Department of Medicine, University of Montreal, Montreal, QC H3T 1J4, Canada.