Non-coding regions are the main source of targetable tumor-specific antigens – DATASETS (k=33)
Creators
- Céline M. Laumont1
- Krystel Vincent1
- Leslie Hesnard1
- Éric Audemard1
- Éric Bonneil1
- Jean-Philippe Laverdure1
- Patrick Gendron1
- Mathieu Courcelles1
- Marie-Pierre Hardy1
- Caroline Côté1
- Chantal Durette1
- Charles St-Pierre1
- Mohamed Benhammadi1
- Joël Lanoix1
- Suzanne Vobecky2
- Elie Haddad2
- Sébastien Lemieux1
- Pierre Thibault1
- Claude Perreault1
- 1. IRIC, Université de Montréal
- 2. CHU Ste-Justine, Université de Montréal
Description
Tumor-specific antigens (TSAs) represent ideal targets for cancer immunotherapy, but few have been identified thus far. We therefore developed a proteogenomic approach to enable the high-throughput discovery of TSAs coded by potentially all genomic regions. In two murine cancer cell lines and seven human primary tumors, we identified a total of 40 TSAs, about 90% of which derived from allegedly non-coding regions and would have been missed by standard exome-based approaches. Moreover, the majority of these TSAs derived from non-mutated yet aberrantly expressed transcripts (such as endogenous retroelements) that could be shared by multiple tumor types. In mice, the efficacy of TSA vaccination was influenced by two parameters that can be estimated in humans and could serve for TSA prioritization in clinical studies: TSA expression and the frequency of TSA-responsive T cells in the pre-immune repertoire. In conclusion, the strategy reported herein could considerably facilitate the identification and prioritization of actionable human TSAs.
Notes
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