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

Autor:	Apavaloaei A; 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., Hesnard L; Institute for Research in Immunology and Cancer (IRIC), University of Montreal, Montreal, QC H3T 1J4, Canada., Hardy MP; Institute for Research in Immunology and Cancer (IRIC), University of Montreal, Montreal, QC H3T 1J4, Canada., Benabdallah B; CHU Sainte-Justine Research Center, Montreal, QC H3T 1C5, Canada., Ehx G; Institute for Research in Immunology and Cancer (IRIC), University of Montreal, Montreal, QC H3T 1J4, Canada., Thériault C; Institute for Research in Immunology and Cancer (IRIC), University of Montreal, Montreal, QC H3T 1J4, Canada., Laverdure JP; Institute for Research in Immunology and Cancer (IRIC), University of Montreal, Montreal, QC H3T 1J4, Canada., Durette C; Institute for Research in Immunology and Cancer (IRIC), University of Montreal, Montreal, QC H3T 1J4, Canada., Lanoix J; Institute for Research in Immunology and Cancer (IRIC), University of Montreal, Montreal, QC H3T 1J4, Canada., Courcelles M; Institute for Research in Immunology and Cancer (IRIC), University of Montreal, Montreal, QC H3T 1J4, Canada., Noronha N; 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., Chauhan KD; Faculty of Health Sciences, Michael G. DeGroote School of Medicine, McMaster University, Hamilton, ON L8N 3Z5, Canada., Lemieux S; Institute for Research in Immunology and Cancer (IRIC), University of Montreal, Montreal, QC H3T 1J4, Canada; Department of Biochemistry and Molecular Medicine, University of Montreal, Montreal, QC H3T 1J4, Canada., Beauséjour C; CHU Sainte-Justine Research Center, Montreal, QC H3T 1C5, Canada; Department of Pharmacology and Physiology, University of Montreal, Montreal, QC H3T 1J4, Canada., Bhatia M; Faculty of Health Sciences, Michael G. DeGroote School of Medicine, McMaster University, Hamilton, ON L8N 3Z5, Canada; Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON L8N 3Z5, Canada., Thibault P; Institute for Research in Immunology and Cancer (IRIC), University of Montreal, Montreal, QC H3T 1J4, Canada; Department of Chemistry, University of Montreal, Montreal, QC H3T 1J4, Canada. Electronic address: pierre.thibault@umontreal.ca., Perreault C; 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. Electronic address: claude.perreault@umontreal.ca.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2022 Aug 16; Vol. 40 (7), pp. 111241.
DOI:	10.1016/j.celrep.2022.111241
Abstrakt:	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. Competing Interests: 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. (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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