Dr Réjean Lapointe, Ph.D.

Full professor;
Department of Medicine;
Université de Montréal, CRCHUM and Institut du cancer de Montréal.

 

Key words: Cancer immunotherapy, B and T lymphocytes, Human Immunology, Cellular therapy, Vaccine development, Breast, lung and kidney cancer, Indolamine 2,3-dioxygenase (IDO), Immune checkpoints, Tumor infiltrating lymphocytes (TIL), BK virus (kidney transplants), Severe burns

Contact :

rejean.lapointe@umontreal.ca

Office: 514-890-8000 x.25489

1987-90  B. Sc., Microbiology, Université Laval

1990-92  M. Sc., Microbiology, Université Laval

1992-97  Ph. D., Biochemistry, Université Laval (Dean’s list, Faculty of Graduate and Postdoctoral Studies)

1997-2001  PDF, National Cancer Institute, National Institutes of Health (USA)

1997-2001   Fellowship from Fogarty International Center (NIH, Bethesda, MD)

2003-2006  FRSQ research fellow: Junior

2005-2009  FRSQ research fellow: Junior 2

2009-2013  FRSQ research fellow: Senior

  • 2016-21  (co-PI) Terry Fox Research Institute (TFRI)
    ‘‘Immunotherapy Translational Research Project (iTNT)’’
  • 2016-18  (co-PI) Merck Investigator Studies Program
    ‘‘Phase II clinical trial evaluating pembrolizumab in combination with carboplatin/paclitaxel as a treatment in unresectable locally advanced or metastatic melanoma’’
  • 2016-19  (co-PI) Merck Investigator Studies Program
    ‘‘A Phase I/II Study of Pembrolizumab in Combination with Nab-Paclitaxel in Patients with Unresectable Stage III or Stage IV Non Small-Cell Lung Carcinoma’’
  • 2016-17  (PI) Fondation des pompiers du Québec
    ‘‘Impact du microbiome sur l’immuno-modulation et -suppression chez les grands brûlés (severely burned patients)’’
  • 2016-17  (PI) Canadian Institutes of Health Research (CIHR)
    ‘‘Injectable thermosensitive hydrogel as delivery vehicle of lymphocytes for cancer immunotherapy’’
  • 2015-17  (PI) FRQ-S Cell therapy network
    ‘‘Microbiome et modulation de la réponse immune anti-tumorale et anti-VIH’’
  • 2015-17  (PI) Concours Fonds Merck Sharp & Dohme
    ‘‘Development of a preventive vaccine against BK virus in transplanted patients’’
  • 2013-16  (PI) CCSRI
    ‘‘Genome-wide transcriptional analysis of intra-tumoral T cell subsets’’
  • 2017 (renewable)  (co-PI) Fond de la recherche Québec – Santé (FRQS)
    ‘‘Breast cancer tissue banking – Cancer Network’’
  • 2012-2017 (PI) Natural Sciences and Engineering Research Council of Canada (NSERC) – Discovery grant
    ‘‘Deciphering alternative functions of B lymphocytes’’

 

Awards and prizes

2000-2001  Fellowship Award for Research Excellence (FARE) from FELCOM (NIH, Bethesda, MD)

1997  Dean’s list, Faculty of Graduate and Postdoctoral Studies (awarded for quality of doctoral thesis)

1995  American Society for Microbiology Student Travel Grant

Human tumour immunotherapy 

Interactions between the immune system and breast, lung and kidney cancer

Tumoral antigens are defined as being proteins expressed exclusively in cancer cells which are not found in normal organ-derived tissues. Many of these antigens were primarily identified in melanoma. In general, these antigens are presented to T lymphocytes as peptides (or epitopes) by the major histocompatibility complex (MHC) class I or II. The initial goal of this project is to identify new tumoural antigens in breast cancer using diverse approaches.

 

In addition, we’re studying the diversity of immune cell populations which infiltrate tumours, as well as mechanisms of intratumoural immunoregulation

 

Clinical immunomonitoring platform

We developed this platform in order to assess the immunological impact of clinical interventions in cancer patients. For example, we evaluate parameters in the blood (flow cytometry, cytokines, chemokines, etc.) and in the tumours (immunofluoresent staining and others) of patients receiving new immunotherapies (anti-PD1, anti-CTLA-4, etc.). We hope to identify predictive and mechanistic biomarkers linked to patient outcomes.

 

Tumour antigen presentation via MHC class II

We are studying the mechanisms governing tumour antigen presentation by MHC class II. This type of presentation leads to CD4+ T lymphocyte activation, which is essential to obtain a cellular immune response. This type of response involved CD8+ T lymphocytes, also called cytotoxic cells as they have the capacity to eliminate target cells, such as cancer cells. 

 

Consequences of indolamine 2,3-dioxygenase (IDO) expression in human cancers

The first generation of immunotherapy clinical trials did lead to some convincing clinical responses, but only in a small percent of patients: to understand this, we must learn more about immunoregulatory mechanisms controlling immunological tolerance to tumours. One potential mechanism could be the protein indolamine 2,3-dioxygenade (IDO) whose function is to catabolise tryptophan and which is capable of locally inhibiting and neutralizing T lymphocytes. We have observed the presence of IDO in human breast and renal cancer tissues. This project consists of defining if IDO expression is frequent and linked to clinical data, identifying cells which produce IDO and determining if T lymphocytes are affected by its presence. If IDO appears to negatively control T lymphocytes and potentially contribute to immune tolerance, than it may represent a viable target to better control this control mechanism.

 

Breast cancer biobank from the Cancer Research Network of the Fonds de recherche en santé du Québec (FRQS)

We manage the CHUM breast cancer tissue bank, a component of the FRQS cancer research network. The bank samples include mononucleated cells from the blood, plasma, tumour samples (cellular lysate, total RNA, and tissue frozen in OCT) and healthy margins when available. More than 2,500 patients have been recruited. The banked samples are available to the scientific community.

 

 

Associated websites:

  1. CRCHUM 

  2.  UdeM webpage

  3. Research Gate  

  4. Twitter  

  5. Linkedin  

  6. Blog  

 

Platforms:

  1. Immunomonitoring (LIST)

  2. Cytométrie de flux (LIST)

 

Pharma Collaborators: 

  • Merck

  • BMS

  • Folia biotech

1. Nicolas Boily (BSc, MSc student, nicolas.boily@umontreal.ca)

2. Stéphanie Lepage (MSc, Research Assistant, niny19@hotmail.com)

3. Anne Monette (PhD, post-doctoral fellow, anne.monette@mail.mcgill.ca)

4. David Possamaï (BSc, PhD student, david.possamai@gmail.com)

5. Paméla Thébault (PhD, Research Associate, pamela.thebault@gmail.com)

6. Zeid Kazbari (BSc, MSc student, zeidkuzbari@hotmail.com)

  1. 2016. Monette, Anne, Caroline Ceccaldi, Elias Assaad, Sophie Lerouge, and Réjean Lapointe, Chitosan thermogels for local expansion and delivery of tumor-specific T lymphocytes towards enhanced cancer immunotherapies, Biomaterials, Jan;75:237-49.

  2. 2015. Reuben, Alexandre, Jessica Godin-Ethier, Manuela M. Santos and Réjean Lapointe, T lymphocyte-derived TNF and IFN-gamma represses HFE expression in cancer cells, Molecular Immunology, 65(2):259-66  

  3. 2014.  Laïla-Aïcha Hanafi, Dominique Gauchat, Jessica Godin-Ethier, Jean-Baptiste Duvignaud, Denis Leclerc, Nathalie Grandvaux, and Réjean Lapointe, Fludarabine down-regulates indoleamine 2,3-dioxygenase in tumors via a proteasome-mediated degradation mechanism, PlosOne, Jun 9;9(6):e99211.

  4. 2014.  Reuben, Alexandre, Mikaël Phénix, Manuela Santos and Réjean Lapointe, The wild-type hemochromatosis protein HFE inhibits MHC I antigen presentation, European Journal of Immunolology, Jun;44(6):1604-14.  

  5. 2012. Galon J, Pagès F, Marincola FM, Angell HK, Thurin M, Lugli A, Zlobec I, Berger A, Bifulco C, Botti G, Tatangelo F, Britten CM, Kreiter S, Chouchane L, Delrio P, Arndt H, Asslaber M, Maio M, Masucci GV, Mihm M, Vidal-Vanaclocha F, Allison JP, Gnjatic S, Hakansson L, Huber C, Singh-Jasuja H, Ottensmeier C, Zwierzina H, Laghi L, Grizzi F, Ohashi PS, Shaw PA, Clarke BA, Wouters BG, Kawakami Y, Hazama S, Okuno K, Wang E, O'Donnell-Tormey J, Lagorce C, Pawelec G, Nishimura MI, Hawkins R, Lapointe R, Lundqvist A, Khleif SN, Ogino S, Gibbs P, Waring P, Sato N, Torigoe T, Itoh K, Patel PS, Shukla SN, Palmqvist R, Nagtegaal ID, Wang Y, D'Arrigo C, Kopetz S, Sinicrope FA, Trinchieri G, Gajewski TF, Ascierto PA, and Fox BA., Cancer classification using the Immunoscore: a worldwide task force., Journal of  Translational Medicine, Oct 3;10:205.  

  6. 2012. Thibodeau, Jacques, Marie-Claude Bourgeois-Daigneault, and Réjean Lapointe Counteracting subversion of MHC class II antigen presentation by tumors, OncoImmunology, Sep 1;1(6):908-916.

  7. 2012. Forget, Marie-Andrée, Yannick Huon, Alexandre Reuben, Cécile Grange, Moïshe Liberman, Jocelyne Martin, Anne-Marie Mes-Masson, Nathalie Arbour and Réjean Lapointe, Stimulation of Wnt/b-catenin pathway in human CD8+ T lymphocytes from blood and lung tumors leads to a shared young/memory phenotype, PLoS One, 7(7):e41074

  8. 2011. Fox BA, Schendel DJ, Butterfield LH, Aamdal S, Allison JP, Ascierto PA, Atkins MB, Bartunkova J, Bergmann L, Berinstein N, Bonorino CC, Borden E, Bramson JL, Britten CM, Cao X, Carson WE, Chang AE, Characiejus D, Choudhury AR, Coukos G, de Gruijl T, Dillman RO, Dolstra H, Dranoff G, Durrant LG, Finke JH, Galon J, Gollob JA, Gouttefangeas C, Grizzi F, Guida M, Hakansson L, Hege K, Herberman RB, Hodi FS, Hoos A, Huber C, Hwu P, Imai K, Jaffee EM, Janetzki S, June CH, Kalinski P, Kaufman HL, Kawakami K, Kawakami Y,Keilholtz U, Khleif SN, Kiessling R, Kotlan B, Kroemer G, Lapointe R, Levitsky HI, Lotze MT, Maccalli C, Maio M, Marschner JP, Mastrangelo MJ, Masucci G, Melero I, Nelief C, Murphy WJ, Nelson B, Nicolini A, Nishimura MI, Odunsi K, Ohashi PS, O'Donnell-Tormey J, Old LJ, Ottensmeier C, Papamichail M, Parmiani G, Pawelec G, Proietti E, Qin S, Rees R, Ribas A, Ridolfi R, Ritter G, Rivoltini L, Romero PJ, Salem ML, Scheper RJ, Seliger B, Sharma P, Shiku H, Singh-Jasuja H, Song W, Straten PT, Tahara H, Tian Z, van Der Burg SH, von Hoegen P, Wang E, Welters MJ, Winter H, Withington T, Wolchok JD, Xiao W, Zitvogel L, Zwierzina H, Marincola FM, Gajewski TF, Wigginton JM, Disis ML (105 authors), Defining the Critical Hurdles in Cancer Immunotherapy, Journal of Translational Medicine Dec 14;9(1):214        

  9. 2011. Godin-Ethier, Jessica, Laïla-Aïcha Hanafi, Ciriaco Piccirillo and Réjean Lapointe, Indoleamine 2,3-dioxygenase expression in human cancer: clinical and immunological parameters correlation, Clinical Cancer Research, Nov 15;17(22):6985-91,   

  10. 2011. Grange, Cécile, Jason Létourneau, Marie-Andrée Forget, Jessica Godin-Ethier, Jocelyne Martin, Moishe Liberman, Matieu Latour, Hugues Widmer, Ciriaco Piccirillo, Jean-Batiste Lattouf, Jean François Cailhier, Réjean Lapointe, Phenotypic characterization and functional analysis of human tumor immune infiltration after mechanical and enzymatic disaggregation, Journal of Immunological Methods, Sep 30;372(1-2):119-26.

  11. 2011. Forget, Marie-Andrée, Alexandre Reuben, Simon Turcotte, Jocelyne Martin and Réjean Lapointe, Polyfunctionality of a DKK1 self antigen-specific CD8+ T lymphocyte clone in lung cancer, Cancer Immunology Immunotherapy, 60(8):1119-25.

  12. 2011. Doucet, Jean-Daniel, Marie-Andrée Forget, Cécile Grange, Nathalie Arbour, Veronika von Messling, and Réjean Lapointe, Presentation of conserved structural influenza proteins by major histocompatibility complexes class I and II in human antigen presenting cells. Journal of General Virology, 92(Pt 5):1162-71.

  13. 2011. Doucet, Jean-Daniel, Dominique Gauchat and Réjean Lapointe. Identification of T cell epitopes by a novel mRNA PCR-based epitope chase technique. Journal of Immunotherapy,34(2):183-186.