En tant que clinicien-chercheur en immunologie pédiatrique, mes recherches visent à mieux comprendre le rôle des cytokines dans la différenciation des cellules T CD8 et à développer de nouvelles approches immunothérapeutiques ciblant les voies de signalisation dépendantes des cytokines et les récepteurs inhibiteurs exprimés sur les lymphocytes T CD8, pour soigner les infections virales chroniques et le cancer. Soutenu par des organismes de financement nationaux (Instituts de Recherche en Santé du Canada, National Institute of Health) et privés (Société de Leucémie et Lymphome du Canada, Société canadienne du Cancer / Fondation Cole, Fondation Charles Bruneau), mon laboratoire a acquis une solide expertise dans le domaine de l’épuisement des lymphocytes T, une voie de différenciation qui limite les fonctions optimales des cellules effectrices et prévient le développement de mémoire. Nous sommes particulièrement impliqués dans l’identification des voies de signalisation et des facteurs de transcription cytokines-dépendants régulant l’épuisement des lymphocytes T durant une infection virale chronique ou un cancer. Nous cherchons en outre à développer de nouvelles immunothérapies combinées qui ciblent les récepteurs inhibiteurs et les voies de signalisation, pour améliorer les taux de guérison des patients avec cancers réfractaires. Enfin, nous avons développé une expertise particulière dans la reconstitution immunitaire de patients atteints de déficit immunitaire combiné sévère traités par greffe de cellules souches, dans le but d’informer sur les meilleures approches thérapeutiques pour traiter ces patients.

Dr. Hélène Decaluwe first completed her medical studies at McGill University (1994-1999) and continued her post-doctoral training in Pediatrics at the University of Montreal (1999-2003). She then pursued her Pediatric Clinical Immunology training in the world-renowned Immunology Unit of Necker-Enfants Malades Hospital in Paris, under the supervision of Alain Fischer (2003-2004). There, she was involved in the diagnosis, treatment and care of children affected by severe immunodeficiency diseases that required hematopoietic stem cell transplantation or gene therapy. In Paris, she also completed a Master’s degree in Immunology (2004-2005) in Jean-Laurent Casanova’s laboratory at the Faculté de Médecine Necker-Enfants Malades where she developed a murine model of complete gamma-interferon receptor deficiency. She then continued her scientific training by a PhD in James Di Santo’s laboratory at the Pasteur Institute (2006-2010). Her thesis project evaluated the role of γc-dependent cytokines in the homeostasis and differentiation of T lymphocytes after an acute viral infection, and was supported by grants from the Canadian Institutes of Health Research in association with Bayer and the Canadian Asthma, Allergy and Immunology Foundation, the Fonds de Recherche du Québec – Santé, l’Association pour la Recherche sur le Cancer – France, and Fondation Canadienne Louis Pasteur.

In 2010, she was appointed an Assistant Professor position in the Department of Pediatrics of the University of Montreal and has integrated the Allergy, Immunology and Rheumatology division of the CHU Sainte-Justine, where she has been working as a Pediatric Immunologist since. Now an Associate Professor, she established her basic science and translational research laboratory at the CHU Sainte-Justine Research Center, and has been training numerous graduate students while being actively involved on multiple committees in the Research Center, in particular as the elected representative of the young investigators (2014-2017). Her laboratory focuses on the role of cytokines in the regulation of T cell differentiation and exhaustion during viral infection and cancer. She is particularly involved in dissecting the mechanisms driving the exhaustion of T and NK cells during chronic viral infection and cancer and on developing new therapeutic approaches to prevent viral or tumor evasion and relapse. She is further involved in basic and translational studies on the immune reconstitution of children treated for severe combined immunodeficiencies by hematopoietic stem cell transplantation, through a large North-American consortium supported by the National Institute of Health (NIH), the Primary Immune Deficiency Treatment Consortium. Her lab is supported by grants from the Canadian Institutes of Health Research (CIHR), the National Institute of Health (NIH, USA), the Fonds de Recherche du Québec – Santé, the Canadian Cancer Society and the Cole Foundation.

1. Beltra JC, Bourbonnais S, Bédard N, Charpentier T, Boulangé M, Michaud E, Boufaied I, Bruneau J, Shoukry N, Lamarre A, Decaluwe H. IL2Rβ-dependent signals drive terminal exhaustion and suppress memory development during chronic viral infection. Proc Natl Acad Sci USA 2016, 113(37):E5444-53.
2. Griffith L, Cowan M, Notarangelo L, Kohn D, Puck J, Shearer W, Burroughs L, Torgerson T, Decaluwe H, Haddad E. Primary Immune Deficiency Treatment Consortium Update. J Allerg Clin Immunol 2016, 138(2) : 375-385.
3. Beltra JC, Decaluwe H. Cytokines and persistent viral infections. Cytokine 2016, 82 : 4-15. (Invited review)
4. Mathieu C, Beltra JC, Charpentier T, Bourbonnais S, Di Santo JP, Lamarre A, Decaluwe H. IL-2 and IL-15 regulate CD8 memory T cell differentiation but are dispensable for protective recall responses. Eur J Immunol 2015, 45(12): 3324-3338.
5. Decaluwe H, Taillardet M, Corcuff E, Munitic I, Law H, Rocha B, Rivière Y, Di Santo JP. Gamma(c) deficiency precludes CD8 T cell memory despite formation of potent T cell effectors. Proc Natl Acad Sci USA 2010 May; 107:9311-9316.
6. Munitic I*, Decaluwe H*, Evaristo C, Wlodarczyk M, Worth A, Le Bon A, Selin LK, Di Santo JP, Borrow P, Rocha B. CD8 subpopulations of different epitope specificities and precursor frequencies have identical differentiation patterns in response to viral infection. J Virol 2009;83 : 11795-11807. * co-first authors
7. Neven B, Leroy S, Decaluwe H, Le Deist F, Picard C, Moshous D, Mahlaoui N, Debré M, Casanova JL, Dal Cortivo L, Madec Y, Hacein-Bey S, de Saint-Basile G, de Villartay JP, Blanche S, Cavazanna-Calvo M, Fischer A. Long-term outcome after haematopoietic stem cell transplantation of a cohort of 90 patients with severe combined immunodeficiency. Blood 2009;113 :4114-24.
8. Masse GX*, Corcuff E*, Decaluwe H, Bommhardt U, Lantz O, Buer J, Di Santo JP. Gamma c cytokines provide multiple homeostatic signals to naïve CD4+ T cells. Eur J Immunol 2007;37 :2602-2616. * co-first authors