CV Science

Patrick LEGEMBRE Onco-immunology

Course and current status

Present address:

• CIRI, UMR CNRS 5308 - Inserm U1111; St Etienne Cedex.
• E-mail: patrick.legembre@inserm.fr or patrick.legembre@univ-st-etienne.fr
• Key works: CD95/Fas, lupus, triple negative breast cancer, inflammation, TNF receptors, apoptosis, calcium.

Education 

• 2007- Habilitation to supervise research (HDR); University of Bordeaux; Immunology/Oncology.
• 2002- Ph.D.; University of Bordeaux; Immunology/Oncology.

Employments

• September 2026- Now: Director of Research Inserm, CIRI, UMR CNRS 5308, Inserm U1111, Faculte de Medecine Jacques Lisfranc, St Priest en Jarez, France.
• Nov 2019- August 2026: Director of Research Inserm, UMR CNRS 7276 - Inserm U1262; Limoges/France. 
• Jan 2010- Oct 2019: Director of Research Inserm (Professor), CLCC Eugène Marquis, Rennes/France.
• Dec 2005-Dec 2009- Charge de Recherche Inserm (Associate professor), UMR CNRS 5164 (Pr. Moreau JF). Bordeaux/France.
• Sept 2002-Oct 2005- Postdoctoral fellow, (Pr Peter M). Ben May Institute For Cancer Research/ University of Chicago. Chicago/USA.

Patents

2010. WO2010063847; 2014. WO2014118317; 2015. WO2015189236; 2015. WO2015044229; 2015. WO2015158810; 2015. WO2015104284; 2017. WO2017149012; 2018. WO2018130679; 2023. WO2023161412A1; 2023. WO2023099578A1

Scientific Academy Society and committees membership

• Member of National Scientific Council CNRS-CSI. Institut des sciences biologiques (INSB) (2024-2029)
• Member of National Ligue Contre Le Cancer Scientific Council (2013-2017)
• Member of National INSERM scientific council-CSS2 (2008-2012)
• Associate editor of the journal Recent Patents on Anti-Cancer Drug Discovery. (2009-2018)
• Editorial board member of Anti-Cancer Drugs (2010-present); Int. J. Oncology (2021-present) and Frontiers in Molecular Medicine (2021-present)

Awards

• 2019: Price “Jean Valade” Fondation de France.
  
• 2016: Price “Ruban Rose Avenir”.
• 2016: Price “Fondation Banque Populaire de l’Ouest Avenir”.
• 2012-2017: Equipe “Ligue Contre Le Cancer”.
• 2007-2012: ANR young scientist.

PUBLICATIONS (10 main publications over 97; according Web of Science h-index:32).

1. Boizard-Moracchini A, Msalbi D, Huot-Marchand S, Haymour L, Lebrault E, Tchen J, Jekel T, Galli G, Brilland B, Mérillon N, Josensi C, Lozano C, Mazars J, Douard M, Danger Y, Vérité F, Barnetche T, Lazaro E, Duffau P, Pfirmann P, Magerus-Chatinet A, Jean M, Augusto JF, Armengaud J, Richez C, Vacher P, Legembre P* and Blanco P*. Soluble CD95L triggers Caspase-10-driven reactive oxygen species production in neutrophils and aggravates anti-neutrophil cytoplasmic antibody-vasculitis. Nature Communications. 2026. doi: 10.1038/s41467-026-74452-8. *Co-Last Authors.
2. Kenji SF, Kurma K, Collet B, Oblet C, Debure L, Di Primo C, Minder L, Vérité F, Danger Y, Jean M, Penna A, Levoin N, Legembre P. MMP7 cleavage of amino-terminal CD95 death receptor switches signaling toward non-apoptotic pathways. Cell Death Dis. 2022. doi: 10.1038/s41419-022-05352-0.
3. Poissonnier A, Guégan JP, Nguyen HT, Best D, Levoin N, Kozlov G, Gehring K, Pineau R,, Jouan F,, Morere L,, Martin S, Thomas M, Lazaro E, Douchet I, Ducret T, van de Weghe P, Blanco P, Jean M, Vacher P and Legembre P. Disrupting the CD95-PLCγ1 interaction prevents Th17-driven inflammation. Nature Chemical Biology. 2018. doi: 10.1038/s41589-018-0162-9.
4. Poissonnier A, Sanséau D, Le Gallo M, Malleter M, Levoin N, Viel R, Morere L, Penna A, Blanco P, Dupuy A, Poizeau F, Fautrel A, Seneschal J, Jouan F, Ritz J, Forcade E, Rioux N, Contin C, Ducret T, Vacher A-M, Barrow PA, Flynn RJ, Vacher P, and Legembre P. CD95-Mediated Calcium Signaling Promotes T Helper 17 Trafficking to Inflamed Organs in Lupus-Prone Mice. Immunity. 2016. doi: 10.1016/j.immuni.2016.06.028. 
5. Malleter M, Tauzin S, Bessede A, Castellano R, Goubard A, Godey F, Levêque J, Jézéquel P, Campion L, Campone M, Ducret T, MacGrogan G, Debure L, Collette Y, Vacher P, Legembre P. CD95L cell surface cleavage triggers a prometastatic signaling pathway in triple-negative breast cancer. Cancer Res. 2013. doi: 10.1158/0008-5472.CAN-13-1794.
6. Khadra N, Bresson-Bepoldin L, Penna A, Chaigne-Delalande B, Ségui B, Levade T, Vacher AM, Reiffers J, Ducret T, Moreau JF, Cahalan MD, Vacher P, Legembre P. CD95 triggers Orai1-mediated localized Ca2+ entry, regulates recruitment of protein kinase C (PKC) β2, and prevents death-inducing signaling complex formation. PNAS. 2011. doi: 10.1073/pnas.1116946108.
7. Tauzin S, Chaigne-Delalande B, Selva E, Khadra N, Daburon S, Contin-Bordes C, Blanco P, Le Seyec J, Ducret T, Counillon L, Moreau JF, Hofman P, Vacher P and Legembre P. The naturally processed CD95L elicits a c-yes/calcium/PI3K-driven cell migration pathway. PLoS Biology. 2011. doi: 10.1371/journal.pbio.1001090.
8. Bénéteau M, Daburon S, Moreau JF, Taupin JL, Legembre P. Dominant-negative Fas mutation is reversed by down-expression of c-FLIP. Cancer Res. 2007 Jan 1;67(1):108-15. doi: 10.1158/0008-5472.CAN-06-1415.
9. Legembre P, Barnhart BC, Zheng L, Vijayan S, Straus SE, Puck J, Dale JK, Lenardo M, Peter ME. Induction of apoptosis and activation of NF-kappaB by CD95 require different signalling thresholds. EMBO Rep. 2004. doi: 10.1038/sj.embor.7400280.
10. Barnhart BC*, Legembre P*, Pietras E, Bubici C, Franzoso G, Peter ME. CD95 ligand induces motility and invasiveness of apoptosis-resistant tumor cells. EMBO J. 2004. doi: 10.1038/sj.emboj.7600325. *Co-First Authors.

CONFERENCE ORGANIZATION

Organizer of International Congress “Cancer Cell Death and Therapy 2017”, St. Malo (France), May 10-12, 2017.

Organizer of 1st International Congress “Cell Death in Cancer”, St. Malo (France), May 13-16, 2012.

Scientific summary

CD95 (also known as Fas) is a member of the tumor necrosis factor receptor (TNFR) superfamily and was originally identified as a death receptor that triggers apoptosis. Its ligand, CD95L (Fas ligand), is a transmembrane cytokine (mCD95L) that can be cleaved by metalloproteases to generate a soluble form (sCD95L) released into the circulation. While membrane-bound CD95L expressed by activated T lymphocytes and NK cells is essential for immune homeostasis by eliminating infected or transformed cells and promoting immune contraction, soluble CD95L acts as a potent pro-inflammatory cytokine. Elevated levels of sCD95L contribute to the development of autoimmune diseases, including systemic lupus erythematosus and ANCA vasculitis and promote metastatic dissemination in triple-negative breast cancer.

Our research aims to elucidate the molecular mechanisms that determine how CD95 signaling switches from apoptosis to non-apoptotic and pro-inflammatory pathways. We seek to identify the immune and non-immune cell populations whose functions are dysregulated by soluble CD95L in cancer and autoimmune diseases, and to exploit this knowledge to develop innovative therapeutic strategies that selectively inhibit the pathogenic, non-apoptotic functions of the CD95/CD95L axis while preserving its essential physiological role in immune surveillance.