Dr Simon Turcotte, M.D., M.Sc.

Assistant Professor of Surgery and Scientist;
Department of Surgery;
Université de Montréal, CHUM Hepato-pancreato-biliary Service,
CRCHUM and Institut du cancer de Montréal

 

Key words: Cancer immunology and immunotherapy, immuno-oncology, adoptive T cell transfer, solid tumors, gastrointestinal cancers, immune profiling, biomarkers, tumor-reactive T cells, tumorantigens, neoantigens. 

 

 

Contact :

simon.turcotte.1@umontreal.ca

Office: 514-890-8000 x.35328

2003, M.D., Université de Montréal, Faculty of Medicine

2008, M.Sc. Biomedical Sciences, Université de Montréal, Faculty of Medicine, Laboratory of Dr Réjean Lapointe

2009, General Surgey, Post-Graduate Medical Studies, Université de Montréal, Faculty of Medicine, Department of Surgery

2012, Post-doctoral Research and Surgical Oncology Fellowship, Surgery Branch, National Cancer Institute, Bethesda, MD, USA, Laboratory of Steven A. Rosenberg.

2013, Hepatobiliary and Pancreatic Surgical Oncology Fellowship, Memorial Sloan-Kettering Cancer Center, New York, NY, USA

2015-2017  FRQS Clinical Research Scholar - Salary Award: Junior 1 

  • 2016-19 (co-PI) Institut du cancer de Montréal (Project Grant)

    "Initiating the CHUM Adaptive T cell immunotherapy program"

  • 2016-18 (PI) Bristol-Myers Squibb (Non-Clinical Research Grant)

    "Defining the molecular determinants of T cell-reactive and non-reactive colorectal cancer liver metastases to overcome resistance to T cell-based immunotherapy"

  • 2016-18 (co-PI) Biotherapeutics for Cancer Treatment - BioCanRx (Catalyst projects)

    "Recombinant TCRs and petide-MHC antibodies to target KRAS hotspot mutations in pancreatic cancer

  • 2015-19 (PI) Fond de recherche Santé -Québec - Junior 1 (Clinical Research Scholar Research Grant)

    "Therapeutic potential of metastatic colon cancer immune recognition"

  • 2014-17 (PI) Canadian Cancer Society Research Institute (Innovation Grant)

    "Harnessing the mutation-reactive T-cell response against metastatic colorectal cancer"

  • 2013-17 (PI) Institut du cancer de Montréal (Start-up funding - Reverse the Brain program)

    "Reconnaissance immunitaire des cancers gastro-intestinaux"

 

Awards and prizes

2013 Junior Investigator Grant Panel Travel Award, Canadian Cancer Society Research Institute (CCSRI)

2012 Fellowship Training Award, Centre hospitalier de l’Université de Montréal (CHUM)

2011 Fellowship Training Award, Department of Surgery, U. of Montreal

2010 Fellowship Training Award, Department of Surgery, U. of Montreal

2009 Fellowship Training Award, Department of Surgery, U. of Montreal

2009 Best Scientific Oral Presentation, 5th annual scientific meeting, Canadian Society for Surgical Oncology (CSSO)

2009 Meilleure présentation scientifique, Department of Surgery, U. of Montreal

2008 Visibility Award, Quebec Medical Association

2007 Resident Research Prize, Canadian Society for Clinical Investigation/Canadian Institutes of Health Research

2007 Travel Award for Scientific Meeting, Department of Surgery 

2007 Best Scientific Presentation, Quebec Surgical Association 

2006 Masters Degree Award, Department of Surgery, U. of Montreal 

2006 Georges-Étienne Cartier Excellence Award for a Surgery Resident, Department of Surgery, U. of Montreal 

2005 Best Oral Scientific Presentation, Fond de recherche santé - Québec/CRCHUM

2005 Canderel Fund Studentship - Institut du cancer de Montréal

2005 Masters Degree Award, Biomedical Science Program U. of Montreal/ CRCHUM

2004 Recognition Award for a Medical Resident, Association of French Language Physicians of Canada

Immune recognition of gastrointestinal cancers

New treatments are needed for people suffering from gastrointestinal (GI) cancers such as liver, pancreatic and colorectal cancers, which are leading causes of cancer-related deaths worldwide.

 

Therapeutic breakthroughs have recently been reported with the use of cancer immunotherapies, which boost immune cells, called T cells, to fight off cancer cells. GI cancers however appear relatively refractory to the first-generation of cancer immunotherapies, for reasons that are not currently well understood.

 

Dr. Turcotte, a cancer immunologist, has found that GI cancer metastases can harbour tumor-reactive T cells. In patients, these T cells are however too few and dysfunctional, unable to control cancer progression in absence of immunotherapy.

 

The general goals of Dr. Turcotte’s team are to develop effective immunotherapy for GI cancers, by:

a) defining a tumor taxonomy based on immunologic features enabling the selection of patients more likely to respond to T cell-based immunotherapies;

 

b) discovering new immune-suppressive pathways that can be targeted to reinvigorate tumor-reactive T cells in patients,

 

c) discovering new types of cancer antigens recognized by T cells that can be targeted with personalized cancer immunotherapy approaches.

 

The team uses high throughput genomics and proteomics combined with biological assays to validate findings. This research is based on the study of well-annotated human biospecimens collected from large cohorts of patients contributing to the CHUM Hepatopancreatobiliary and Colorectal Cancer (CRC) Clinical Database & Biobank.

Current projets and techniques used:

  1. Immune taxonomy of CRC liver metastases. CRC remains the 2nd leading cause of cancer-related death in both men and women in Western countries. We are investigating 400 CRC liver metastases resected in a cohort of 230 patients by high throughput proteomics and genomics to define patient subgroups with more/less immunogenic metastatic CRC and to identify key immune-suppressive pathways at play in liver metastases.

    • Tissue microarrays and RNA sequencing

    • Automated quantification of multiplexed immunohistochemistry and fluorescence

    • Tumor-infiltrating T cell gain/loss of function assays

  2. Identification of antigens derived from somatic cancer mutations (neoantigens) and recognized by T cells in patients with metastatic CRC. How often could functional neoantigen-reactive T cells be isolated and used for adoptive cell transfer in patients with metastatic CRC? Is there a rationale to justify the development of personalized vaccination targeting neoantigens to prevent relapse of CRC?

    • Whole exome, RNA, and peptide sequencing of CRC liver metastases

    • Autologous antigen-presenting cells expressing candidate neoantigens to screen for reactivity of tumor-infiltrating CD4+ and CD8+ T cells

    •  T cell-receptor cloning and sequencing

    • Functional characterization of tumor-reactive T cell clones by multiplexed-PCR (Fluidigm), multiplexed cytokine secretion (Mesoscale), and lysis assays 

  3. Building a compendium of T cell-receptors (TCRs) reactive to oncogenic KRAS codon 12 mutations. KRAS is a frequently mutated gene driving the progression of pancreatic and colorectal cancers. We are screening these patients for mutated KRAS-reactive CD4+ and CD8+ T cells. The goal is to clone as many TCRs reactive to mutated-KRAS epitopes presented in the context of as many type I and II HLAs. The vision is to enable the development of adoptive cell transfer of T cells engineered to express KRAS-reactive TCRs personalized to patient HLAs and specific KRAS cancer mutations. 

    • RNA sequencing of tumors for KRAS mutation status and HLA-typing

    • Peptide-cleavable tetramers and autologous antigen-presenting cells expressing mutated KRAS to screen for reactivity of autologous T cells

    • TCR sequencing, cloning and affinity characterization

  4. Frequency and function of CD4+ tumor-infiltrating lymphocytes (TIL) reactive to metastatic GI cancers refractory to chemotherapy. Limited data support that CD4+ “helper T cells” reactive to common epithelial cancers are spontaneously generated in vivo in humans. We are taking advantage of having generated 13 cancer cell lines from GI cancer metastases and expanded TIL from the same metastases to investigate whether CD4+ T cells can be harnessed for cancer immunotherapy. 

    • Ex-vivo detection, expansion and cloning of CD4+ TIL reactive to autologous cancer cell lines

    • TCR cloning and functional characterization of tumor-reactive CD4+ TIL. 

 

Associated websites:

  1. CRCHUM's profile 

  2. Research Gate

 

 Platforms: 

  1.  Chief, CHUM Hepatopancreatobiliary and Colorectal Cancer Clinical Database & Biobank

 

Pharma Collaborators:

 

1. Mélissa Mathieu (Ph.D., post-doctoral fellow, melissa.mathieu@umontreal.ca) 

2. David Henault (M.Sc. candidate. david.henault@ umontreal.ca)

3. Sandy Pelletier (Research assistant, scientific coordinator, adoptive T cell therapy program, sandy.pelletier@umontreal.ca)

4. Alexandre Paradis (M.Sc., technician, alex.19.paradis@gmail.com)

5. Louise Rousseau (Technician & data manager, louise.rousseau.chum@ssss.gouv.qc.ca)

6. Sophie Langevin (Data manager, sophie.langevin.chum@ssss.gouv.qc.ca) 

  1. Tran E, Ahmadzadeh M, Lu YC, Gros A, Turcotte S, Robbins PF, Gartner JJ, Zheng Z, Li YF, Ray S, Wunderlich JR, Somerville RP, Rosenberg SA. Immunogenicity of somatic mutations in human gastrointestinal cancers. Science 2015;350:1387-90 

  2. Balachandran V, Arora A, Gonen M, Ito H, Turcotte S, Shia J, Viale A, Snoeren N, van Hooff SR, Borel Rinkes IH, Adam R, Kingham TP, Allen PJ, Dematteo RP, Jarnagin WR, D'Angelica MI. A validated prognostic multigene expression assay for overall survival in resected colorectal cancer liver metastases. Clin Cancer Res 2016;22:2575-2582

  3. Maker AV, Ito H, Mo Q, Weisenberg E, Qin LX, Turcotte S, Maithel SK, Shia J, Blumgart L, Fong Y, Jarnagin WR, Dematteo RP, D'Angelica MI. Genetic evidence that intratumoral T-cell proliferation and activation is associated with recurrence & survival in patients with resected colorectal liver metastases. Cancer Immunol Res 2015;3:380-8

  4. Tran E, Turcotte S, Gros A, Robbins PF, Lu W, Dudley ME, Wunderlich JR, Sommerville RP, Hogan K, Hinrichs CS, Parkhurst MR, Yang JC, Rosenberg SA. Cancer immunotherapy based on mutation-specific CD4+ T cells in a patient with metastatic epithelial cancer. Science 2014;344:641-5

  5. Gros A. Robbins PF, Yao X, Li YF, Turcotte S, Tran E, Wunderlich JR, Mixon A, Farid S, Dudley ME, Hanada K, Almeida JR, Darko S, Douek DC, Yang JC, Rosenberg SA.  PD-1 identifies the patient-specific CD8+ tumor-reactive repertoire infiltrating human tumors. J Clin Invest 2014;124:2246-59

  6. Turcotte S, Katz SC, Shia J, Jarnagin WR, Kingham TP, Allen PJ, Fong Y, D’Angelica MI, DeMatteo RP. Tumor MHC class I expression improves the prognostic value of T-cell density in resected colorectal liver metastases.Cancer Immunol Res 2014;2:530-7

  7. Turcotte S, Gros A, Tran E, Wunderlich JR, Lee C-CR, Phan GQ, Yang JC, Robbins PF, Dudley ME, Rosenberg SA. Tumor-reactive CD8+ T cells in metastatic gastrointestinal cancer refractory to chemotherapy. Clin Cancer Res 2014;20:331-43.

  8. Turcotte S, Gros A, Hogan K, Tran E, Hinrichs CS, Wunderlich JR, Dudley ME, Rosenberg SA. Phenotype and function of T cells infiltrating visceral metastases from gastrointestinal cancers and melanoma: implications for adoptive cell transfer therapy. J Immunol 2013;191:2217-25

  9. Gros A, Turcotte S, Wunderlich JR, Ahmadzadeh M, Dudley ME, Rosenberg SA. Myeloid cells obtained from the blood but not from the tumor can suppress T-cell proliferation in patients with melanoma.  Clin Cancer Res 2012;18:5212-23

  10. Turcotte S, Forget M-A, Beauseigle D, Nassif E, Lapointe R. PDEF overexpression is associated with nodal metastasis and hormone receptor positivity in invasive breast cancer. Neoplasia 2007;9:788-96

    Complete list oh published work in MyBiobliography.