Gregory Ehx

Dr. Ehx and his team study how leukemic cells are recognized by immune cells or how they escape from their surveillance. One of the aims of their research is to create immunotherapies promoting the permanent eradication of leukemia. A second aim is to improve current therapies by maximizing the immune recognition of cancer cells surviving the treatment.

Research theme

Cancer results from the transformation of healthy cells into abnormal cells proliferating without regulation. The capacity of immune cells to eradicate cancer cells is now well-established. In particular, T cells have the remarkable capacity to specifically recognize and kill malignant cells without harming normal cells. This recognition is mediated by the interaction of the T-cell receptor with peptides presented by the MHC molecules of malignant cells. However, cancer cells can also express inhibitory molecules preventing immune cells from working effectively. Studying how T cells recognize cancer cells and how cancer cells defend themselves against T cells is the key to unlocking new anti-cancer treatments based on immune cells.

Acute myeloid leukemia (AML) is an aggressive form of blood cancer and is the most frequent form of leukemia in adults. The nature of the MHC peptides and immuno-inhibitory molecules expressed by AML cells is at the center of the research efforts of Dr. Ehx and his collaborators. Their work has resulted in the development of BamQuery, a computational tool enabling the identification of the most tumor-specific MHC peptides (1). By using this tool, and a home-made proteogenomic approach, they have shown that the most immunogenic MHC peptides of AML derive from aberrantly expressed genomic regions such as introns, endogenous retroelements, or non-coding RNAs (2). They also found that leukemic cells presenting the highest levels of these peptides also expressed high levels of immuno-inhibitory molecules, such as PD-L1 or CD47.

More recently, Gregory and his colleagues found that the expression of endogenous retroelements, possibly coding for immunogenic peptides, is enhanced by the hypomethylating agent 5-azacytidine, a treatment frequently used in AML (3). However, they also found that 5-azacytidine induced an unfolded protein response and subsequent autophagy in these cells, and that autophagy degraded the transcripts of endogenous retroelements. Their work could pave the way to using autophagy inhibitors to maximize the immune recognition of AML cells treated with 5-azacytidine.

The team

Selected publications

1. Ruiz-Cuevas MV, Hardy MP, Larouche JD, Apavaloaei A, Kina K, Vincent K, Gendron P, Laverdure JP, Durette C, Thibault P, Lemieux S, Perreault C, Ehx G.
   BamQuery: a proteogenomic tool to explore the immunopeptidome and prioritize actionable tumor antigens
   Genome Biology 2023
2. Ehx G, Larouche JD, Durette C, Laverdure JP, Hesnard L, Vincent K, Hardy MP, Thériault C, Rulleau C, Lanoix J, Bonneil E, Feghaly A, Apavaloaei A, Noronha N, Laumont CM, Delisle JS, Vago L, Hébert J, Sauvageau G, Lemieux S, Thibault P, Perreault C.
   Atypical acute myeloid leukemia-specific transcripts generate shared and immunogenic MHC class-I-associated epitopes
   Immunity 2021
3. Noronha N, Durette C, Cahuzac M, E Silva B, Courtois J, Humeau J, Sauvat A, Hardy MP, Vincent K, Laverdure JP, Lanoix J, Baron F, Thibault P, Perreault C, Ehx G.
   Autophagy degrades immunogenic endogenous retroelements induced by 5-azacytidine in acute myeloid leukemia
   Leukemia 2024

Funding

Related content

⇒ Resistant cells and leukemia: Grégory Ehx receives a MIS grant from the FNRS 
⇒ Three researchers honored by the Belgian Royal Academy of Medicine
⇒ The Comte de Launoit prize awarded to Gregory Ehx
⇒ Four ULiège projects selected for Welbio Investigator Program funding
⇒ Developing a vaccine to destroy cancer cells that survive chemotherapy 
⇒ Inhibiting autophagy to enhance immune recognition of azacitidine-treated leukemia 
⇒ Grégory Ehx appointed FNRS Research associate at the University of Liège 
⇒ Ontwerp van een vaccin om terugval van acute myeloïde leukemie te voorkomen
⇒ A program to assist in designing anti-cancer vaccines

Contact

Hematology lab
Building B34, GIGA +4 room 4/30B
Avenue de l'Hopital, 1
4000 Liège
Belgium
Email: g.ehx@uliege.be
Tel: +32(0)366.47.33